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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

An Episode of Psychosis After Nitrous Oxide Abuse During a Pandemic: A Case Report.

The abuse of inhalants like nitrous oxide (N2O), readily available worldwide, has remained a prominent public health problem during the last few decades. Literature reveals increased use during the previous pandemic, particularly regarding recreational use. There is limited evidence-based data available to relate the abuse of N2O with psychosis. Therefore, this case report of a 22-year-old adult with no previous psychiatry history, reportedly abusing 75-100 canisters of N2O per day during the last pandemic COVID-19 lockdown, highlights the relationship between (N2O) abuse and the symptoms evolved including delusions, auditory hallucinations, and disorganized cognition. All the laboratory findings and results from imaging modalities were inconsistent for any organic cause of the symptoms. The case then underwent treatment with antipsychotic medications and a multidisciplinary model, which improved the symptoms gradually. The case, in particular, discusses N2O abuse, which is widespread in European Union countries, including the UK and the Republic of Ireland, and its chronic use puts one at a higher risk of developing psychosis, personality changes, affective lability, anxiety, depression, cognitive impairment, and myeloneuropathy. The sale of N2O for its psychoactive properties is prohibited in many countries, including the Republic of Ireland, as per legislation. However, N2O is not a controlled drug, meaning it is not a crime to possess N2O. This case report manifests the psychopathy caused by abuse of N2O, which would further attract specialists in the field to conduct epidemiological studies for prevention at the primary level.

Real World Evidence asthma and COPD inhaled treatment therapy in Spain.

Background: This study aimed to describe the use of pressured metered dose inhalers (pMDI) and dry powder inhalers (DPI) in Spanish patients in terms of socio-demographic, clinical, and functional characteristics in patients with asthma or COPD on maintenance treatment with inhaled therapy. Methods: A retrospective, descriptive, national, multicentre, and observational study using a database with 1.8 million patients from hospitals and primary care centers as a secondary information source. Results: The sample included 24,102 subjects with asthma on maintenance therapy (26.0% with pMDI, 54.9% with DPI, and 19.0% with a combination of DPI + pMDI inhalers) and 12,858 subjects with COPD on maintenance therapy (26.1% with pMDI, 38.7% with DPI and 35.2% with a combination of pMDI + DPI inhalers, mostly extemporary triple therapy). In proportion, subjects ≥ 75 years old use more pMDI than DPI, while younger subjects (40-64 years old) use more DPI. An inhalation chamber was prescribed in 51.0% of asthma subjects and 47.2% of COPD subjects treated with pMDI. The use of an inhalation chamber increases with the degree of airflow limitation by disease and age. In subjects with comorbidities, pMDI inhaler use increased in those ≥75 years old for asthma and COPD subjects. Switching from pMDI to DPI and vice versa was relatively common: 25.5% of asthma subjects and 21.9% of COPD subjects treated with pMDI had switched from DPI in the previous year. On the contrary, 14.1% and 11.7% of asthma and COPD patients treated with DPI had switched from pMDI the last year. Conclusions: The use of pMDI or DPI can vary according to age, both in asthma and COPD. Switching from pMDI to DPI and vice versa is relatively common. Despite the availability of dual and triple therapy inhalers on the market, a considerable number of subjects were treated with multiple devices.

Targeting LINC070974 inhibits lung adenocarcinoma cell proliferation and progression by interacting with Y-box binding protein 1.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Increasing evidence suggests that long noncoding RNAs play crucial roles in lung cancer pathogenesis. We previously identified a novel lncRNA, LINC070974, which is associated with tumor cell proliferation. In the present study, we find that knockdown of LINC070974 inhibits cell proliferation, migration and invasion as well as tumor formation both in vitro and in nude mice. LINC070974 silencing also improves cisplatin efficacy in A549/DDP cells. The function of LINC070974 may depend on its interaction with YBX1. Knockdown of LINC070974 reduces the recruitment of YBX1 to the CCND1 promoter and delays tumor progression through its coregulatory genes, which are mainly involved in the p53 signaling pathway. We utilize nebulized inhalation to deliver siRNAs targeting LINC070974 and find that LINC070974 significantly prevents tumor metastasis and growth in lung tissues. These findings reveal the role of LINC070974 in lung cancer and suggest a promising therapeutic approach involving siRNA inhalation.

A National Mandate for Thermal Fuses for Home Oxygen Users is Cost-effective in the Prevention of Burn Morbidity, Mortality and Property Loss.

Smoking while using home oxygen leads to explosions which cause cutaneous burns, death, and loss of property. Thermal fuses interrupt the propagation of ignited oxygen-lines and reduce the risk of injury. Prior to mandating thermal fuses for all home oxygen users in the US, cost-effectiveness analysis should be performed. A Markov model was constructed for suffering thermal injury while smoking on home oxygen. Societal and Medicare perspectives were adopted evaluating the costs of a federal policy including purchasing/shipping thermal fuses to all home oxygen users. Costs included the healthcare required to treat burn patients and extending lives in advanced chronic obstructive pulmonary disease. Cost savings included the avoided property loss. Effectiveness was measured in gains in quality adjusted life years (QALYS). In the status quo, the 10-year societal cost was $28.67 billion compared to $28.36 billion in the policy mandate (saving $305.40 million at ten years). 1,812 QALYs were gained with the policy mandate, yielding and ICER of -$160,317. For the Medicare payor perspective, the incremental cost-effectiveness ratio (ICER) was $64,981. Deterministic and probabilistic sensitivity analyses showed little variation in the ICER under multiple scenarios. The discrepancy between the dominant ICER for societal perspective and cost-effective ICER for Medicare perspective reflected savings from averted property loss not realized by Medicare. A national policy mandating and paying for thermal fuses for all home oxygen users is dominant from a societal perspective and cost-effective from a Medicare perspective. The US government should adopt such a policy.

Adherence to inhaled corticosteroid therapy and treatment escalation in the Swedish adult asthma population.

BACKGROUND: Patients with uncontrolled asthma should be evaluated for medication adherence. This study aimed to identify characteristics associated with poor adherence to inhaled corticosteroids (ICS) and to explore adherence prior to treatment escalation. METHODS: This nationwide longitudinal cohort study included adult asthma patients (n = 30880) with a healthcare visit including Asthma Control Test (ACT) and registered in the Swedish National Airway Register between 1 July 2017 and 28 February 2019 (index date). Patient data was crosslinked to other national registers. Treatment steps two years pre- and one year post-index, were identified by prescribed drugs. Poor adherence was defined as Medication Possession Ratio <80 %. RESULTS: Poor adherence was identified in 73 % of patients in treatment steps 2-5, where of 35 % had uncontrolled asthma (ACT≤19). In adjusted models, poor adherence was associated with better disease control; ACT≤19 (OR 0.78, 95 % CI 0.71-0.84), short-acting ß2-agonist (SABA) overuse (0.69, 0.61-0.79) and exacerbations (0.79, 0.70-0.89) in steps 2-3. Among patients with uncontrolled asthma, poor adherence was associated with SABA overuse (1.71, 1.50-1.95), exacerbations (1.29, 1.15-1.46), current smoking (1.38, 1.21-1.57) and inversely associated with asthma management education (0.85, 0.78-0.93. Similar results were observed in steps 4-5. When investigating post-index treatment, 53 % remained stationary, 30 % stepped down and 17 % escalated treatment. Prior to escalation, 49 % had poor adherence. CONCLUSIONS: Poor ICS adherence was associated with better asthma control. Among uncontrolled patients, poor adherence was associated with SABA overuse and exacerbations. Our result highlights the importance of asthma management education to improve adherence in uncontrolled patients.

Intravenous Tobramycin Inhalation for Patients With Advanced Bronchiectasis With Pseudomonas aeruginosa Infection in Home Medical Care: A Report of Two Cases.

Home medical care faces limitations in the number of doctor and nurse visits, availability of medical devices, and economic factors, making daily injections difficult for in-home patients. We describe two cases of advanced bronchiectasis with Pseudomonas aeruginosa infection treated with inhaled tobramycin in a home setting, demonstrating clinical effectiveness. Using commercially available empty eye drop containers to prepare an aseptic inhalation solution and nebulizers easily usable at home, our experience suggests that this could be a viable therapeutic alternative in home medical care.

Monitoring cystic fibrosis airway infections with Pseudomonas aeruginosa with anti-OprF serum antibodies.

BACKGROUND: The management of cystic fibrosis (CF) requires knowledge of the patient's microbiological status. The serology of anti-Pseudomonas aeruginosa antibodies against exoenzymes or water-soluble antigens has gained diagnostic value, particularly to detect the onset of colonization with P. aeruginosa. However, the diversity and variable expression of these antigens, which was unknown when the ELISAs became common diagnostic procedures at CF clinics, prohibits the quantitative evaluation of bacterial antigen load during intermittent and chronic infection. METHODS: An ELISA was developed to measure the serum IgG antibody levels against P. aeruginosa porin OprF, a species-specific, conserved, immunogenic and constitutively expressed protein present in the outer membrane and extracellular vesicles. RESULTS: Serial serum samples were collected from 310 people with CF (pwCF) over a period of up to 15 years. Compared to a reference of P. aeruginosa - negative CF sera set to 1, OprF antibody titers ranged from 0.3 to 13.2 (median: 1.7) in 56 intermittently colonized patients and from 0.5 to 51.2 (median: 11.8) in 176 chronically colonized pwCF showing higher anti-OprF antibody levels during chronic than during intermittent colonization with P. aeruginosa (P = 0, Z = - 21.7, effect size 0.62). Inhalation with twice daily 80 mg tobramycin decreased OprF antibody titers (P = 5 × 10-5), particularly during the third and fourth year of chronic colonization. CONCLUSION: The OprF ELISA should be an appropriate tool to monitor Pseudomonas serology at all stages of infection and disease severity and to study the impact of short- and long-term therapeutic interventions.