Evaluation of airborne asbestos concentrations associated with the maintenance of brakes on an industrial overhead crane.

OBJECTIVES: To evaluate potential airborne asbestos exposures during brake maintenance and repair activities on a P&H overhead crane, and during subsequent handling of the mechanic's clothing. METHODS: Personal (n = 27) and area (n = 61) airborne fiber concentrations were measured during brake tests, removal, hand sanding, compressed air use, removal and reattachment of chrysotile-containing brake linings, and reinstallation of the brake linings. The mechanic's clothing was used to measure potential exposure during clothes handling. RESULTS: All brake linings contained between 19.9% to 52.4% chrysotile asbestos. No amphibole fibers were detected in any bulk or airborne samples. The average full-shift airborne chrysotile concentration was 0.035 f/cc (PCM-equivalent asbestos-specific fibers, or PCME). Average task-based personal air samples collected during brake maintenance, sanding, compressed air use, and brake lining removal tasks ranged from 0 to 0.48 f/cc (PCME). The calculated 30-minute time-weighted average (TWA) airborne chrysotile concentration associated with 5-15 minutes of clothes handling was 0-0.035 f/cc PCME. CONCLUSION: The results indicated that personal and area TWA fiber concentrations measured during all crane brake maintenance and clothes handling tasks were below the current OSHA 8-h TWA Permissible Exposure Limit for asbestos of 0.1 f/cc. Further, no airborne asbestos fibers were measured during routine brake maintenance tasks following the manufacturer's maintenance manual procedures. All short-term airborne chrysotile concentrations measured during non-routine tasks were below the current 30-minute OSHA excursion limit for asbestos of 1 f/cc. This study adds to the available data regarding chrysotile exposure potential during maintenance on overhead cranes.

Severity of inhalation injury and risk of nosocomial pneumonia: a retrospective cohort study.

BACKGROUND: The impact of inhalation injury on risk of nosocomial pneumonia, an important complication in burn patients, is not well established. RESEARCH QUESTION: Is more severe inhalation injury associated with increased risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of patients with suspected inhalation injury admitted to a regional burn center from 2011 to 2022 who underwent diagnostic bronchoscopy within 48 hours of admission. We estimated the association of high-grade inhalation injury (abbreviated injury score [AIS] 3-4) versus low-grade inhalation injury (AIS 1-2) with nosocomial pneumonia (NP) adjusted for age, burn size, and comorbid obstructive lung disease. Death and hospital discharge were considered competing risks. RESULTS: Of the 245 patients analyzed, 51 (21%) had high-grade injury, 180 (73%) had low-grade injury, and 14 (6%) had no inhalation injury. Among the 236 patients hospitalized for >48 hours, NP occurred in 24/50 (48%) patients in the high-grade group, 54/172 (31%) in the low-grade group, and 2/14 (14%) in the no inhalation injury group. High-grade (vs low-grade) inhalation injury was associated with higher hazard of NP in both the proportional cause-specific hazard model (CSHR 2.04; 95% CI, 1.26-3.30; p=0.004) and Fine-Gray subdistribution hazards model (SHR for NP, 2.24; 95% CI, 1.38-3.64; p=0.001). INTERPRETATION: Among patients with inhalation injury, more severe injury was associated with higher hazard of NP in competing risk analysis. Additional research is needed to investigate mechanisms that may explain the relationship between inhalation injury and NP and to identify more effective prevention strategies.

Integration of mucus and its impact within in vitro setups for inhaled drugs and formulations: Identifying the limits of simple vs. complex methodologies when studying drug dissolution and permeability.

Traditionally, developing inhaled drug formulations relied on trial and error, yet recent technological advancements have deepened the understanding of 'inhalation biopharmaceutics' i.e. the processes that occur to influence the rate and extent of drug exposure in the lungs. This knowledge has led to the development of new in vitro models that predict the in vivo behavior of drugs, facilitating the enhancement of existing formulation and the development of novel ones. Our prior research examined how simulated lung fluid (SLF) affects the solubility of inhaled drugs. Building on this, we aimed to explore drug dissolution and permeability in lung mucosa models containing mucus. Thus, the permeation of four active pharmaceutical ingredients (APIs), salbutamol sulphate (SS), tiotropium bromide (TioBr), formoterol fumarate (FF) and budesonide (BUD), was assayed in porcine mucus covered Calu-3 cell layers, cultivated at an air liquid interface (ALI) or submerged in a liquid covered (LC) culture system. Further analysis on BUD and FF involved their transport in a mucus-covered PAMPA system. Finally, their dissolution post-aerosolization from Symbicort® was compared using 'simple' Transwell and complex DissolvIt® apparatuses, alone or in presence of porcine mucus or polymer-lipid mucus simulant. The presence of porcine mucus impacted both permeability and dissolution of inhaled drugs. For instance, permeability of SS was reduced by a factor of ten in the Calu-3 ALI model while the permeability of BUD was reduced by factor of two in LC and ALI setups. The comparison of dissolution methodologies indicated that drug dissolution performance was highly dependent on the setup, observing decreased release efficiency and higher variability in Transwell system compared to DissolvIt®. Overall, results demonstrate that relatively simple methodologies can be used to discriminate between formulations in early phase drug product development. However, for more advanced stages complex methods are required. Crucially, it was clear that the impact of mucus and selection of its composition in in vitro testing of dissolution and permeability should not be neglected when developing drugs and formulations intended for inhalation.

Remission of hypersensitivity pneumonitis after allogeneic hematopoietic stem cell transplantation.

A 50-year-old man was diagnosed with hypersensitivity pneumonitis caused by the environment of his bar owing to worsening symptoms, laboratory test results, and computed tomography images after an environmental inhalation challenge test. His hypersensitivity pneumonitis exacerbated despite receiving prednisolone 20 mg/day. The patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor for myelodysplastic syndrome. No exacerbation of hypersensitivity pneumonitis was observed after HSCT. An environmental inhalation challenge test involving exposure to his bar confirmed the remission of hypersensitivity pneumonitis after HSCT. This case demonstrates that hypersensitivity pneumonitis can be remitted by HSCT.

Toxicity and biokinetics following pulmonary exposure to aluminium (aluminum): A review.

During the manufacture and use of aluminium (aluminum), inhalation exposure may occur. We reviewed the pulmonary toxicity of this metal including its toxicokinetics. The normal serum/plasma level based on 17 studies was 5.7 ± 7.7µg Al/L (mean ± SD). The normal urine level based on 15 studies was 7.7 ± 5.3µg/L. Bodily fluid and tissue levels during occupational exposure are also provided, and the urine level was increased in aluminium welders (43 ± 33µg/L) based on 7 studies. Some studies demonstrated that aluminium from occupational exposure can remain in the body for years. Excretion pathways include urine and faeces. Toxicity studies were mostly on aluminium flakes, aluminium oxide and aluminium chlorohydrate as well as on mixed exposure, e.g. in aluminium smelters. Endpoints affected by pulmonary aluminium exposure include body weight, lung function, lung fibrosis, pulmonary inflammation and neurotoxicity. In men exposed to aluminium oxide particles (3.2µm) for two hours, lowest observed adverse effect concentration (LOAEC) was 4mg Al2O3/m3 (= 2.1mg Al/m3), based on increased neutrophils in sputum. With the note that a similar but not statistically significant increase was seen during control exposure. In animal studies LOAECs start at 0.3mg Al/m3. In intratracheal instillation studies, all done with aluminium oxide and mainly nanomaterials, lowest observed adverse effect levels (LOAELs) started at 1.3mg Al/kg body weight (bw) (except one study with a LOAEL of ~0.1mg Al/kg bw). The collected data provide information regarding hazard identification and characterisation of pulmonary exposure to aluminium.

Effect of airflow rate on droplet deposition of an impinging-jet inhaler in the human respiratory tract.

This paper presents a numerical investigation to understand the transport and deposition of sprays emitted by an impinging-jet inhaler in the human respiratory tract under different inhalation flow rates. An injection model is used for the numerical simulations considering the spreading angles of the spray in the two directions, which are measured from experiments. The model parameter is adjusted to match the mean droplet size measured in the previous experiment. A time-varying sinusoidal inhalation flow rate is utilized as airflow conditions, which is closer to the actual situation when using an inhaler. The results demonstrate that the inhalation airflow rate significantly affects the spray's transport behavior and deposition results in the respiratory tract. Both excessively high and low inhalation flow rates lead to an increase in deposition in the mouth-throat. A moderate inhalation flow rate reduces throat deposition while maximizing lung deposition. Higher inhalation flow rates enable faster delivery of the droplets to the lungs, whereas lower inhalation flow rates achieve a more uniform deposition over time in the lungs. The amount of deposition in different parts of the lung lobes follows a fixed order. This study provides valuable insights for optimizing the inhalation flow rate conditions of the impinging-jet inhaler for clinical applications.

Pulmonary administration of cross-linked chitosan nanoparticles of genistein for regulating blood glucose.

The research study focused on the development and characterization of sustained release formulation of genistein (GEN)-loaded chitosan (CS) nanoparticles to deliver in the form of dry powder inhaler (DPI) via pulmonary route to offer higher stability and anti-diabetic activity. The GEN-loaded nanoparticles were prepared by cross-linking reaction of CS and sodium hexametaphosphate (SHMP). The optimized formulation displayed particle size (PS) of 684.2 ± 26.5 nm, zeta potential (ZP) of 19.6 ± 4.50 mV, % entrapment efficiency (% EE) of 87.33 ± 8.46 % and drug release profile of 85.48 ± 5.50 % for 48 h. The in-vivo studies exhibited a superior sustained release formulation of GEN in the regulation of blood glucose levels (BGLs). The powder showed the emitted fraction (EF) of 86.76 % and effective inhalation index (EI) of 85.41 %. The reduction of BGLs (85 %) was observed in the diabetic group. This might be due to the inhibition of proliferation of pancreatic ß-cells (growth factor inhibition targeting cAMP and ERK1/2 pathway), antioxidative activity, reducing insulin resistance, and the adipose tissue mass and alteration of the hepatic glucose metabolism. Hence, these results proved the delivery of GEN in the form of DPI system as a favorable route for treating type-1 diabetes mellitus with a longer duration of action.

Impact of Pharmacist-Led Intervention on Adherence to Inhalers, Inhalation Technique, and Disease Control Among Asthma/COPD Patients in a Resource Limited Center: An Interventional Study.

Background: Asthma and Chronic obstructive pulmonary disease (COPD) are chronic respiratory conditions characterized by airflow obstruction and respiratory symptoms. Adherence to prescribed inhaler therapy and correct inhalation technique are essential for effective disease management and optimal disease control. However, non-adherence and incorrect inhalation technique are common challenges faced by patients with asthma and COPD, leading to suboptimal treatment outcomes and increased healthcare burden. Purpose: To study the impact of a pharmacist-led intervention on inhaler adherence, inhalation technique, and disease control among patients with asthma and COPD. Patients and Methods: A pre-post interventional design assessed the effects of pharmacist-led intervention on inhaler adherence, inhalation techniques, and disease control in asthma and COPD patients at Dhulikhel Hospital in Nepal. Inclusion criteria: adult patient clinically diagnosed with asthma or COPD patients of all genders. The intervention comprised counseling patients with aids like videos, and informational leaflets. Impact was measured using checklist method for inhalation technique, the Test of Adherence to Inhaler (TAI) questionnaire for adherence to inhaler, and "Asthma Control Test (ACT)" or "COPD Assessment Test (CAT)" for disease control. Results: The pharmacist-led intervention significantly increased adherence to inhalers, evidenced by a notable rise in the proportion of patients with good adherence (P<0.001). Sporadic, deliberate, and unwitting noncompliance pattern also improved significantly after the intervention (P<0.001, P<0.001 and P=0.001). Inhalation technique exhibited substantial improvement after intervention (P<0.001). The analysis indicated significant moderate negative correlations between "TIA" and "CAT" [ρ=-0.31; P=0.01], and between "inhalation technique score" and "CAT score" [ρ=-0.31; P=0.01] suggesting that as adherence to inhaler usage and inhalation technique improve, CAT scores tend to decrease, indicating reduced disease impact on the patient. Conclusion: This study shows the potential efficacy of pharmacist-led intervention in enhancing adherence to inhaler, inhalation technique, and disease control in respiratory conditions such as asthma and COPD.

Macrophage-targeted versus free calcitriol as host-directed adjunct therapy against Mycobacterium tuberculosis infection in mice is bacteriostatic and mitigates tissue pathology.

Host-directed therapy (HDT) with vitamin D in tuberculosis (TB) is beneficial only if the subject is deficient in vitamin D. We investigated pulmonary delivery of 1,25-dihydroxy vitamin D3 (calcitriol) in mice infected with Mycobacterium tuberculosis (Mtb). We made two kinds of dry powder inhalations (DPI)- soluble particles or poly(lactide) (PLA) particles. We compared treatment outcomes when infected mice were dosed with a DPI alone or as an adjunct to standard oral anti-TB therapy (ATT). Mice infected on Day 0 were treated between Days 28-56 and followed up on Days 57, 71, and 85. Neither DPI significantly reduced Mtb colony forming units (CFU) in the lungs. Combining DPI with ATT did not significantly augment bactericidal activity in the lungs, but CFU were 2-log lower in the spleen. CFU showed a rising trend on stopping treatment, sharper in groups that did not receive calcitriol. Lung morphology and histology improved markedly in animals that received PLA DPI; with or without concomitant ATT. Groups receiving soluble DPI had high mortality. DPI elicited cathelicidin, interleukin (IL)-1 and induced autophagy on days 57, 71, and 85. Macrophage-targeted calcitriol is therefore bacteriostatic, evokes innate microbicidal mechanisms, and mitigates pathology arising from the host response to Mtb.

Reducing transient severe motion artifacts of gadoxetate disodium-enhanced MRI by oxygen inhalation: effective for pleural effusion but not ascites.

OBJECTIVES: To evaluate the efficacy of low-flow oxygen inhalation in mitigating transient severe motion (TSM) artifacts associated with gadoxetate disodium-enhanced hepatic magnetic resonance imaging (MRI). METHODS: Patients undergoing gadoxetate disodium-enhanced MRI were included. During the examination, the experimental group received oxygen at 2 L/min via nasal cannula, while the control group did not. Images and TSM scores were evaluated and compared across precontrast, arterial, venous, and hepatobiliary phases. Subgroup analyses were conducted based on the presence of pleural effusion or ascites. RESULTS: A total of 325 patients were included. The motion scores were highest in the arterial phase and lowest in the hepatobiliary phase in both groups, but were significantly lower in the experimental group (p < 0.05). The incidence of TSM was significantly lower in the experimental group (3.29%) compared to the control group (13.29%, p = 0.01). While pleural effusion was associated with reduced image quality in both groups (p < 0.05), the image quality in the pleural effusion category was higher in the experimental group than in the control group. Oxygen inhalation showed limited efficacy in mitigating TSM related to ascites. CONCLUSIONS: Low-flow oxygen inhalation can effectively reduce the occurrence of gadoxetate disodium-related TSM. Pleural effusion may impair respiratory function and contribute to TSM, which can be alleviated by oxygen supplementation. However, Oxygen inhalation is less effective under the condition of ascites.

The Impact of Hydrogen Inhalation Therapy on Blood Reactive Oxygen Species Levels: A Randomized Controlled Study.

Reactive Oxygen Species (ROS) play a key role in physiological processes. However, the imbalance between ROS and antioxidants in favor of the former causes oxidative stress linked to numerous pathologies. Due to its unique attributes, including distinguished permeability and selective antioxidant capability, molecular hydrogen (H2) has become an essential therapeutic agent. Hydrogen Inhalation Therapy (HIT) has come to light as a promising strategy to counteract oxidative stress. In this randomized controlled study, we aimed to evaluate the effectiveness of HIT in reducing blood ROS levels. 37 participants with elevated ROS levels (d-ROMs value > 350 U.CARR) were enrolled in the study. Participants were divided into test and control groups. The test group participants received HIT, and then their blood ROS levels were measured immediately post-treatment and after 24 hours. Their results were compared to those of the control group participants who did not undergo HIT. The test group demonstrated a significant reduction in blood ROS levels after the treatment. These findings suggested the efficacy of HIT in reducing oxidative stress.

Genotoxicity of Formaldehyde: Effect of Whole-Body Exposure on Polychromatic Erythrocyte/Normochromatic Erythrocyte Ratio in Male and Female Rats.

Every day, millions of individuals are exposed to formaldehyde (FA) due to its extensive presence and versatile use. Many in vivoand in vitroexperiments revealed that the mechanism of genotoxicity induced by FA exposure is complex yet toxicity upon whole-body exposure (WBE) to FA is less. As teachers, students, and skilled assistants in the health care sectors are also extensively exposed to FA vapors, it might result in genotoxicity. However, the effects of subchronic exposure to FA at low concentrations are not clear. Hence, analysis of the micronucleus (MN) was necessary to study the genetic toxicity triggered by FA in the bone marrow of male and female experimental rats. The present study is a gender- and duration of exposure-based assessment of the geno- and cytotoxicity in bone marrow cells of Wistar rats to study the effect of WBE to 10% FA on polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio and micronucleated polychromatic erythrocytes (MnPCE) in experimental rats. The obtained result clearly showed that WBE to FA for 60 days at concentrations between 1 and 1.1 ppm (0, 1, and 1.5 h) induced genotoxic effects in both male and female rats by altering the MnPCE% and significantly increasing the ratio of PCE/NCE (1.07 ± 0.23, 1.20 ± 0.20, 1.22 ± 0.14). The PCE/NCE ratio in male rats was lesser (0.98, 1.12, and 1.18) when compared with female rats (1.17, 1.29, and 1.26) with 0, 1, and 1.5 h exposure, respectively. Thus, the genetic/cellular sensitivity to FA differs among the sexes and also depends on the exposure duration.

Real time monitoring of carbon dioxide levels in surgical helmet systems worn during hip and knee arthroplasty.

Background: Orthopaedic surgical helmet systems (SHS) rely on an intrinsic fan to force clean external air over the wearer. Carbon dioxide (CO2) is produced through aerobic metabolism and can potentially accumulate inside the SHS. Levels above 2500 ppm have previously been shown to affect cognitive and practical function. Maximum Health and Safety Executive (HSE) 8-h exposure limit is 5000 ppm. There is a paucity of data on real-world CO2 levels experienced during arthroplasty surgery whilst wearing a SHS. Objectives: To determine intra-operative levels of CO2 experienced within SHS. Methods: CO2 levels were continuously recorded during 30 elective arthroplasties, both primary and revision. Data was recorded at 0.5Hz throughout the procedure utilising a Bluetooth CO2 detector, worn inside a surgical helmet worn with a toga gown. Five surgeons contributed real time data to the study. Results: The average CO2 level across all procedures was 3006 ppm, with 23 of the cases measured within the surgeons' helmets having a mean above 2500 ppm, but none having a mean above 5000 ppm. For each procedure, the time spent above 2500 and 5000 ppm was calculated, with the means being 72.6 % and 5.4 % respectively. Minimum fan speed was associated with only a marginally higher mean CO2 value than maximum fan speed. Discussion: The use of surgical helmet systems for elective orthopaedic surgery, can result in CO2 levels regularly rising to a point which may affect cognitive function. Conclusion: Further research is needed to corroborate these findings however, we recommend that future designs of SHS include active management of exhaust gases, possibly returning to Charnley's original design principles of the body exhaust system.

Lower or higher oxygenation targets in the intensive care unit: an individual patient data meta-analysis.

PURPOSE: Optimal oxygenation targets for patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are not clearly defined due to substantial variability in design of previous trials. This study aimed to perform a pre-specified individual patient data meta-analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) and the Handling Oxygenation Targets in coronavirus disease 2019 (COVID-19) (HOT-COVID) trials to compare targeting a partial pressure of arterial oxygen (PaO2) of 8-12 kPa in adult ICU patients, assessing both benefits and harms. METHODS: We assessed 90-day all-cause mortality and days alive without life support in 90 days using a generalised mixed model. Heterogeneity of treatment effects (HTE) was evaluated in 14 subgroups, and results graded using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN). RESULTS: At 90 days, mortality was 40.4% (724/1792) in the 8 kPa group and 40.9% (733/1793) in the 12 kPa group (risk ratio, 0.99; 95% confidence interval [CI] 0.92-1.07; P = 0.80). No difference was observed in number of days alive without life support. Subgroup analyses indicated more days alive without life support in COVID-19 patients targeting 8 kPa (P = 0.04) (moderate credibility), and lower mortality (P = 0.03) and more days alive without life support (P = 0.02) in cancer-patients targeting 12 kPa (low credibility). CONCLUSION: This study reported no overall differences comparing a PaO2 target of 8-12 kPa on mortality or days alive without life support in 90 days. Subgroup analyses suggested HTE in patients with COVID-19 (moderate credibility) and cancer (low credibility).

H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.

Propofol total intravenous anesthesia vs. sevoflurane inhalation anesthesia: Effects on post­operative cognitive dysfunction and inflammation in geriatric patients undergoing laparoscopic surgery.

Propofol total intravenous anesthesia (TIVA) or sevoflurane inhalation anesthesia (IA) affects post-operative cognitive dysfunction in geriatric patients undergoing laparoscopic surgery; however, relevant real-world clinical evidence on the matter is limited. The present study aimed to compare the effects of propofol TIVA and sevoflurane IA on post-operative cognitive dysfunction in the aforementioned type of patients. The present prospective study enrolled 197 geriatric patients undergoing laparoscopic surgery. Patients were assigned to the propofol TIVA group (n=97) and sevoflurane IA group (n=100) according to the actual anesthesia regimens. The mini-mental state examination (MMSE) score was assessed before surgery and on day (D)1, D3 and D7 following surgery in both groups. The MMSE score on D1 was higher in the TIVA group compared with the IA group (P=0.006). The change in the MMSE scores from before surgery to D1 (P<0.001), D3 (P=0.011) and D7 (P=0.003) was smaller in the TIVA group vs. the IA group. Multivariate linear regression analyses suggested that the anesthesia method of TIVA (vs. IA) was independently related to the increased MMSE score on D1 (b=0.803; P=0.001) and D7 (b=0.472; P=0.025). The levels of interleukin (IL)-17A, IL-6 and tumor necrosis factor-α on D1, D3 and D7 exhibited a slightly decreasing trend in the TIVA group vs. the IA group, although the difference was not statistically significant (all P>0.05). Notably, the levels of IL-17A before surgery (P=0.015), on D3 (P=0.016) and D7 (P=0.002), as well as those of IL-6 on D1 (P=0.027), were negatively associated with the MMSE score at the corresponding time points. Overall, the present study demonstrates that propofol TIVA ameliorates post-operative cognitive dysfunction on D1 compared with sevoflurane IA and exerts a potentially suppressive effect on inflammation in geriatric patients undergoing laparoscopic surgery.

[Long terme oxygen therapy in chronic respiratory diseases]. / Oxygénothérapie à long terme dans les pathologies respiratoires chroniques.

LONG TERM OXYGEN THERAPY IN CHRONIC RESPIRATORY DISEASES. Survival of severe chronic respiratory failure with chronic obstructive pulmonary disease (COPD) is improved by long-term oxygen therapy. Other benefits exist for COPD and other causes of chronic respiratory failure. The indications for this restrictive (more 15 hours per day) treatment require measurements of arterial blood gases in adults. Several actors are involved: the specialist for the prescription, the service provider for supplying and maintaining the equipment, the patient and his entourage, the referring doctor to ensure that oxygen therapy is well tolerated and used. The referring doctor can prescribe short-term oxygen therapy for transient respiratory failure. The choice of oxygen source depends on the patient's ability to ambulate and the required flow rate. Concentrators are increasingly used, despite limited flow rate with mobile devices. Liquid oxygen makes it possible to deliver high flow rates but is expensive. The main complications of oxygen therapy are the worsening of chronic hypercapnia, burns (especially in active smokers)...

OXYGÉNOTHÉRAPIE À LONG TERME DANS LES PATHOLOGIES RESPIRATOIRES CHRONIQUES. La survie des patients souffrant de bronchopneumopathie chronique obstructive (BPCO) insuffisants respiratoires chroniques (IRC) sévères est améliorée par l'oxygénothérapie à long terme (OLT). D'autres bénéfices existent pour les patients IRC. Les indications de ce traitement contraignant (plus de 15 heures par jour) imposent des mesures des gaz du sang artériel chez l'adulte. Plusieurs acteurs sont impliqués : le spécialiste pour la prescription, le prestataire de service pour la fourniture et l'entretien du matériel, le patient et son entourage, le médecin traitant pour s'assurer que l'oxygénothérapie est bien tolérée et utilisée. Le médecin traitant peut prescrire une oxygénothérapie de court terme. Le choix de la source d'oxygène dépend des possibilités de déambulation du patient et du débit requis. Les concentrateurs électriques sont de plus en plus utilisés malgré des débits limités avec les appareils mobiles. L'oxygène liquide permet de délivrer des débits importants mais reste coûteux. Les principales complications de l'oxygénothérapie sont l'aggravation d'une hypercapnie chronique, des brûlures (surtout chez le fumeur actif)...

Qualitative Interviews Exploring Adverse Event Mitigation Strategies in Adults Receiving Amikacin Liposome Inhalation Suspension.

INTRODUCTION: This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS). METHODS: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants' descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants' ratings of strategies' effectiveness. Concept saturation was also assessed. RESULTS: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population. CONCLUSIONS: This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.

Ambient Particulate Matter Induces In Vitro Toxicity to Intestinal Epithelial Cells without Exacerbating Acute Colitis Induced by Dextran Sodium Sulfate or 2,4,6-Trinitrobenzenesulfonic Acid.

Inflammatory bowel disease (IBD) is an immunologically complex disorder involving genetic, microbial, and environmental risk factors. Its global burden has continued to rise since industrialization, with epidemiological studies suggesting that ambient particulate matter (PM) in air pollution could be a contributing factor. Prior animal studies have shown that oral PM10 exposure promotes intestinal inflammation in a genetic IBD model and that PM2.5 inhalation exposure can increase intestinal levels of pro-inflammatory cytokines. PM10 and PM2.5 include ultrafine particles (UFP), which have an aerodynamic diameter of <0.10 µm and biophysical and biochemical properties that promote toxicity. UFP inhalation, however, has not been previously studied in the context of murine models of IBD. Here, we demonstrated that ambient PM is toxic to cultured Caco-2 intestinal epithelial cells and examined whether UFP inhalation affected acute colitis induced by dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid. C57BL/6J mice were exposed to filtered air (FA) or various types of ambient PM reaerosolized in the ultrafine size range at ~300 µg/m3, 6 h/day, 3-5 days/week, starting 7-10 days before disease induction. No differences in weight change, clinical disease activity, or histology were observed between the PM and FA-exposed groups. In conclusion, UFP inhalation exposure did not exacerbate intestinal inflammation in acute, chemically-induced colitis models.