Search

Although the adverse effects of long-term oral corticosteroid use are well-recognised, the risks associated with short courses of steroids, or steroid "bursts", are less frequently acknowledged. With the growing availability of targeted immune therapies, the safety of short course steroid prescriptions warrants greater scrutiny. This review synthesises evidence on the adverse effects of short courses of steroids, finding that even a single burst can increase the risk of several adverse effects including sepsis, cardiovascular events, gastrointestinal bleeding and mood changes. These adverse effects appear to be transient in nature, with the highest risk occurring within 30 days and attenuating over the subsequent 90-180 days. Additionally, this review found a cumulative dose-response relationship, demonstrating that more than 1g or four short courses in a lifetime is associated with heightened risk of several long-term adverse effects. Non-systemic corticosteroids generally exhibit fewer clinically significant adverse effects, although the increased risk of respiratory infections associated with inhaled corticosteroid use should be considered in our tuberculosis-endemic setting. This review highlights the importance of considering a patient's total and cumulative steroid exposure and prescribing steroid bursts only when clearly indicated. Clinicians are encouraged to consider non-steroidal or targeted therapies as safer alternatives wherever possible. [ABSTRACT FROM AUTHOR]

Background: The use of inhaled antibiotics for treating pneumonia in invasively ventilated patients offers a direct approach, allowing for high local concentrations of the drug in the lower respiratory tract while simultaneously reducing systemic toxicity. However, the real efficacy and safety of nebulized antibiotics remain unclear. The aim of the present is to assess among critically adult patients with pneumonia and invasive ventilation, whether receiving adjuvant inhaled antibiotics improves the rate of microbiological eradication. Methods: A comprehensive literature search of randomized clinical trials (RCTs) was conducted (from inception until September 20, 2024, PROSPERO-CRD592906) across Medline, Embase, and Scopus. Randomized controlled trials, enrolling intensive care units (ICU) patients with pneumonia and comparing nebulized antimicrobial therapy (inhaled group) with intravenous antimicrobial treatment or intravenous antimicrobial therapy plus inhaled placebo (control group), were included. The primary outcome was the rate of microbiological eradication after treatment. Secondary outcomes were the rate of clinical recovery, the incidence of drug-related adverse events, ICU and hospital mortality. A qualitative analysis was conducted according to the GRADE framework. Data were pooled using an odds-ratio analysis. The heterogeneity and reliability of our results were evaluated using the I2-statistic and trial sequential analysis (TSA), respectively. Results: A total of 11 RCTs (1472 patients) met the inclusion criteria. Compared to controls, the use of adjuvant inhaled antibiotics determined a greater rate of microbiological eradication (OR 2.63, 95% CI 1.36–5.09; low certainty of evidence). The TSA confirmed the reliability of our primary outcome. Moreover, nebulized antibiotics increased the risk of bronchospasm (OR 3.15, 95% CI 1.33–7.47; high evidence), while nephrotoxicity, clinical recovery, ICU and hospital survival (either in the case of pneumonia caused by MDR bacteria or not) were not different between groups. Conclusions: In conclusion, compared to the sole intravenous therapy, the use of adjuvant inhaled antibiotics for treatment of pneumonia in invasively ventilated critically ill patients was associated with a greater incidence of microbiological eradication (low GRADE and high risk of publication bias), but not with clinical recovery and survival. [ABSTRACT FROM AUTHOR]

Airways, alveoli and the pulmonary tissues are the most vulnerable to the external environment including occasional deliberate or accidental exposure to highly toxic chemical gases. However, there are many effective protective mechanisms that maintain the integrity of the pulmonary tissues and preserve lung function. Alveolar macrophages form the first line of defense against any pathogen or chemical/reactant that crosses the airway mucociliary barrier and reaches the alveolar region. Resident alveolar macrophages are activated or circulating monocytes infiltrate the airspace to contribute towards inflammatory or reparative responses. Studies on response of alveolar macrophages to noxious stimuli are rapidly emerging and alveolar macrophage are also being sought as therapeutic target. Here such studies have been reviewed and put together for a better understanding of the role pulmonary macrophages in general and alveolar macrophage in particular play in the pathogenesis of disease caused by chemical induced acute lung injury. [ABSTRACT FROM AUTHOR]

Background: Increasing awareness of the potential environmental impact of volatile anaesthetic agents has stimulated increased use of total i.v. anaesthesia. However, consolidated comparative evidence of the environmental impact of anaesthetic agents across the whole life cycle is lacking. Methods: We performed a systematic review and narrative evidence synthesis of the environmental impact of anaesthetic agents stratified by drug life cycle. We searched MEDLINE (PubMed), Excerpta Medica dataBASE (EMBASE), Cumulative index to nursing and allied health literature (CINAHL), and DrugBank, from inception until 05 March 2023, for studies describing the environmental impact of anaesthetic drugs on the WHO essential medicine list. Independent review and data extraction were performed by pairs of reviewers. Data on any aspect of cradle-to-grave life cycle analysis were reported, with narrative synthesis grouped according to life cycle domains. Results: From 15 229 records, 42 unique reports met our inclusion criteria. The predominant environmental impact of inhalation anaesthetic agents is atmospheric release, contributing to global warming. This may be improved with the emergence of more efficacious scavenging and capture systems. Packaging and waste contributed most to the environmental impact of i.v. anaesthetic agents. There is increasing concern over the ecological impact of i.v. agents entering water sources, either by disposal of unused medication or through the excretion of drug post-administration. Conclusions: There is increasing concern about the global warming impact of inhalation anaesthetic agents. However, there are insufficient ‘cradle-to-grave’ comparative analyses of the environmental impact of i.v. and inhalation anaesthesia to form evidence-based conclusions. Further research is urgently needed to guide clinical practice.

Airways, alveoli and the pulmonary tissues are the most vulnerable to the external environment including occasional deliberate or accidental exposure to highly toxic chemical gases. However, there are many effective protective mechanisms that maintain the integrity of the pulmonary tissues and preserve lung function. Alveolar macrophages form the first line of defense against any pathogen or chemical/reactant that crosses the airway mucociliary barrier and reaches the alveolar region. Resident alveolar macrophages are activated or circulating monocytes infiltrate the airspace to contribute towards inflammatory or reparative responses. Studies on response of alveolar macrophages to noxious stimuli are rapidly emerging and alveolar macrophage are also being sought as therapeutic target. Here such studies have been reviewed and put together for a better understanding of the role pulmonary macrophages in general and alveolar macrophage in particular play in the pathogenesis of disease caused by chemical induced acute lung injury.

BackgroundPrior to the COVID-19 pandemic, cannabis use social practices often involved sharing prepared cannabis (joints/blunts/cigarettes) and cannabis-related paraphernalia. Previous studies have demonstrated that sharing paraphernalia for cannabis, tobacco, and crack cocaine is a risk factor for respiratory viral and bacterial infections. Although COVID-19 is a respiratory viral infection that spreads through droplets and airborne transmission, it is unclear if many individuals adopted harm reduction practices around sharing cannabis. This study: quantifies the prevalence of sharing prepared non-medical cannabis and cannabis-related paraphernalia reported before and during the pandemic; assesses changes in sharing of non-medical cannabis from before to during the pandemic; assess the association between frequency of non-medical cannabis use and sharing of cannabis during the pandemic; and describes how respondents obtained their cannabis and the reasons for changing their cannabis use during the pandemic to explain differences in sharing patterns.MethodsThis cross-sectional study used data collected from an anonymous, US-based web survey on cannabis-related behaviors from August to September 2020 (n = 1833). Participants were included if they reported using a mode of inhalation for non-medical cannabis consumption. We calculated proportional changes in sharing cannabis before/during the COVID-19 pandemic. Associations between frequency of cannabis use and cannabis sharing during the COVID-19 pandemic were assessed using logistic regression analysis.ResultsOverall, 1,112 participants reported non-medical cannabis use; 925 (83.2%) reported a mode of cannabis inhalation. More respondents reported no sharing during (24.9%) than before the pandemic (12.4%; p

Abstract Background Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease. Methods In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension. Results Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33). Conclusion In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. Trial registration (NCT03873298, MOH_2018-04-24_002331).

Background: Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease. Methods: In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension. Results: Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33). Conclusion: In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. Trial registration: (NCT03873298, MOH_2018-04-24_002331). [ABSTRACT FROM AUTHOR]

Abstract Background Prior to the COVID-19 pandemic, cannabis use social practices often involved sharing prepared cannabis (joints/blunts/cigarettes) and cannabis-related paraphernalia. Previous studies have demonstrated that sharing paraphernalia for cannabis, tobacco, and crack cocaine is a risk factor for respiratory viral and bacterial infections. Although COVID-19 is a respiratory viral infection that spreads through droplets and airborne transmission, it is unclear if many individuals adopted harm reduction practices around sharing cannabis. This study: quantifies the prevalence of sharing prepared non-medical cannabis and cannabis-related paraphernalia reported before and during the pandemic; assesses changes in sharing of non-medical cannabis from before to during the pandemic; assess the association between frequency of non-medical cannabis use and sharing of cannabis during the pandemic; and describes how respondents obtained their cannabis and the reasons for changing their cannabis use during the pandemic to explain differences in sharing patterns. Methods This cross-sectional study used data collected from an anonymous, US-based web survey on cannabis-related behaviors from August to September 2020 (n = 1833). Participants were included if they reported using a mode of inhalation for non-medical cannabis consumption. We calculated proportional changes in sharing cannabis before/during the COVID-19 pandemic. Associations between frequency of cannabis use and cannabis sharing during the COVID-19 pandemic were assessed using logistic regression analysis. Results Overall, 1,112 participants reported non-medical cannabis use; 925 (83.2%) reported a mode of cannabis inhalation. More respondents reported no sharing during (24.9%) than before the pandemic (12.4%; p

BackgroundCurrently, there are no guidelines or consensus statements about the usage of inhaled mucoactive drugs in pediatric respiratory disease conditions from an Indian perspective.ObjectiveTo develop a practical consensus document to help pediatricians in clinical decision-making when choosing an appropriate mucoactive drug for the management of specific respiratory disease conditions.MethodsA committee of nine experts with significant experience in pediatric respiratory disease conditions and a microbiological expert constituted the panel. An electronic search of the PubMed/MEDLINE, Cochrane Library, Scopus, and Embase databases was undertaken to identify relevant articles. Various combinations of keywords such as inhaled, nebulized, mucoactive, mucolytic, mucokinetic, expectorants, mucoregulators, mucociliary clearance, respiratory disorders, pediatric, cystic fibrosis (CF), non-CF bronchiectasis, acute wheezing, asthma, primary ciliary dyskinesia (PCD), critically ill, mechanical ventilation, tracheomalacia, tracheobronchomalacia, esophageal atresia (EA), tracheoesophageal fistula (TEF), acute bronchiolitis, sputum induction, guideline, and management were used. Twelve questions were drafted for discussion. A roundtable meeting of experts was conducted to arrive at a consensus. The level of evidence and class of recommendation were weighed and graded.ConclusionsInhaled mucoactive drugs (hypertonic saline, dry powder mannitol, and dornase alfa) can enhance mucociliary clearance in children with CF. Experts opined that hypertonic saline could be beneficial in non-CF bronchiectasis, acute bronchiolitis, and PCD. The current state of evidence is inadequate to support the use of inhaled mucoactive drugs in asthma, acute wheezing, tracheomalacia, tracheobronchomalacia, and EA with TEF.

Hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP) due to difficult-to-treat-resistant (DTR) Gram-negative bacteria, contributes significantly to morbidity and mortality in ICUs. In the era of COVID-19, the incidences of secondary nosocomial pneumonia and the demand for invasive mechanical ventilation have increased dramatically with extremely high attributable mortality. Treatment options for DTR pathogens are limited. Therefore, an increased interest in high-dose nebulized colistin methanesulfonate (CMS), defined as a nebulized dose above 6 million IU (MIU), has come into sight. Herein, the authors present the available modern knowledge regarding high-dose nebulized CMS and current information on pharmacokinetics, clinical studies, and toxicity issues. A brief report on types of nebulizers is also analyzed. High-dose nebulized CMS was administrated as an adjunctive and substitutive strategy. High-dose nebulized CMS up to 15 MIU was attributed with a clinical outcome of 63%. High-dose nebulized CMS administration offers advantages in terms of efficacy against DTR Gram-negative bacteria, a favorable safety profile, and improved pharmacokinetics in the treatment of VAP. However, due to the heterogeneity of studies and small sample population, the apparent benefit in clinical outcomes must be proven in large-scale trials to lead to the optimal use of high-dose nebulized CMS. [ABSTRACT FROM AUTHOR]

The role of inhaled antifungals for prophylaxis and treatment of invasive fungal pneumonias remains undefined. Herein we summarize recent clinically relevant literature in high-risk groups such as neutropenic hematology patients, including those undergoing stem cell transplant, lung and other solid transplant recipients, and those with sequential mold lung infections secondary to viral pneumonias. Although there are several limitations of the available data, inhaled liposomal amphotericin B administered 12.5 mg twice weekly could be an alternative method of prophylaxis in neutropenic populations at high risk for invasive fungal pneumonia where systemic triazoles are not tolerated. In addition, inhaled amphotericin B has been commonly used as prophylaxis, pre-emptive, or targeted therapy for lung transplant recipients but is considered as a secondary alternative for other solid organ transplant recipients. Inhaled amphotericin B seems promising as prophylaxis in fungal pneumonias secondary to viral pneumonias, influenza, and SARS CoV-2. Data remain limited for inhaled amphotericin for adjunct treatment, but the utility is feasible. [ABSTRACT FROM AUTHOR]

Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections. [ABSTRACT FROM AUTHOR]

IntroductionAsthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a. statins), suggest a therapeutic role in chronic inflammatory lung diseases. However, despite positive laboratory investigations and promising epidemiological data, clinical trials using statins for the treatment of asthma have yielded conflicting results. Inadequate statin levels in the airway compartment could explain these findings. Areas covered: HMGCR is in the mevalonate (MA) pathway and MA signaling is fundamental to lung biology and asthma. This article will discuss clinical trials of oral statins in asthma, review lab investigations relevant to the systemic versus inhaled administration of statins, address the advantages and disadvantages of inhaled statins, and answer the question: is there a role for inhaled statins in the treatment of asthma? Expert commentary: If ongoing investigations show that oral administration of statins has no clear clinical benefits, then repurposing statins for delivery via inhalation is a logical next step. Inhalation of statins bypasses first-pass metabolism by the liver, and therefore, allows for delivery of significantly lower doses to the airways at greater potency. Statins could become the next major class of novel inhalers for the treatment of asthma.

The aim of this study was to evaluate safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of a novel inhaled formulation of voriconazole (ZP-059). In the single ascending dose part, 4 cohorts of 6 healthy subjects received one dose of inhaled voriconazole (5-40 mg). In the multiple ascending dose part, 3 cohorts of 6 subjects with mild asthma received voriconazole 10 mg twice daily [BID], 20 mg BID or 40 mg once daily. In the 2-period crossover part, 16 subjects with mild to moderate asthma each received one dose of inhaled voriconazole 20 mg and one dose of oral voriconazole 200 mg. A bioanalytical method was developed and validated to simultaneously determine concentrations of voriconazole and its metabolite N-oxide voriconazole in serum and sputum. Inhaled voriconazole was well tolerated with no treatment emergent adverse events (TEAEs) leading to treatment discontinuation. The PK profile of inhaled voriconazole showed rapid absorption, apparent greater than proportional increase in exposure with increasing dose, a consistent half-life across dosing, and large clearance and volume of distribution. Following repeat administration limited accumulation was observed. Systemic exposure following inhaled voriconazole was much lower than following oral voriconazole. Serum data confirmed that voriconazole was extensively metabolized also when administered by inhalation. Sputum data following inhaled voriconazole were limited but demonstrated increasing exposure with increasing dose. The current study shows the newly developed dry powder inhaled formulation of voriconazole to be safe and well tolerated, providing a possible improved treatment approach for patients affected by allergic bronchopulmonary aspergillosis. Trial Registration: ClinicalTrials.gov ID: NCT04229303., (© 2025 Zambon S.P.A. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Diseases of the pulmonary alveolus, such as pulmonary fibrosis, are leading causes of morbidity and mortality, but exceedingly few drugs are developed for them. A major reason for this gap is that after inhalation, drugs are quickly whisked away from alveoli due to their high perfusion. To solve this problem, the mechanisms by which nano‐scale drug carriers dramatically improve lung pharmacokinetics using an inhalable liposome formulation containing nintedanib, an antifibrotic for pulmonary fibrosis, are studied. Direct instillation of liposomes in murine lung increases nintedanib's total lung delivery over time by 8000‐fold and lung half life by tenfold, compared to oral nintedanib. Counterintuitively, it is shown that pulmonary surfactant neither lyses nor aggregates the liposomes. Instead, each lung compartment (alveolar fluid, alveolar leukocytes, and parenchyma) elutes liposomes over 24 h, likely serving as “drug depots.” After deposition in the surfactant layer, liposomes are transferred over 3–6 h to alveolar leukocytes (which take up a surprisingly minor 1–5% of total lung dose instilled) in a nonsaturable fashion. Further, all cell layers of the lung parenchyma take up liposomes. These and other mechanisms elucidated here should guide engineering of future inhaled nanomedicine for alveolar diseases.

Background: Asthma is a common disease especially in kids. The development of asthma symptoms appears to involve a combination of genetic predisposition and environmental factors. There are many medicines for asthma management, the most important of which is corticosteroid. High doses of inhaled corticosteroids can be associated with hyperglycemia risk increase. Aim of the work: To detect the effect of inhaled corticosteroids on blood glucose homeostasis in asthmatic children. Patients and Methods:This study was conducted at pediatric inpatient and outpatient clinic of New Damietta Al-Azhar University Hospital in the period from September 2018 to September 2019, included 90 asthmatic children chosen randomly, 55 of them were males and 35 of them were females, aged from 2 to 12 years, For each child, the demographic data were collected, divided into three groups according to type of treatment, group I [using ICS only for more than 3 months], group II [using SCS] and group III [using ICS & SCS]. Results: Regarding WBCs and its differentiation there was a significant increase in WBCs [7.8±2.1] and eosinophil [2.7±0.83] in [group III] more than [group I]; WBCs [5.8±2.2] and eosinophil [1.4±0.6] and [group II]; WBCs [6.4±2.0] and eosinophil [1.5±0.7]. Regarding blood glucose, [group I] mean value was [89.6±22.8]; [group II] was [91.6±17.3]; [group III] was [104.4±36.1]. There was statistically significant difference between group I with III and group II with III [P2: 0.032 and P3: 0.043]. Conclusion: Blood glucose level increased in children using both inhaled and systemic corticosteroids and it was significant statistically.

OBJECTIVE This study evaluates the value of inhaled budesonide (BUD) administration in neonatal respiratory distress syndrome (RDS) cases especially for near-term neonates. METHODS A randomized controlled trial involving 120 neonates with respiratory distress, which was diagnosed as RDS, was conducted from July 2016 to March 2018. The neonates studied were divided into 2 groups: group 1 (the inhaled BUD group), consisting of 60 neonates who received BUD (2 mL, 0.25-mg/mL suspension) inhalation, twice daily for 5 days; and group 2 (the placebo group), consisting of 60 neonates with RDS who received humidified distilled sterile water inhalation (2 mL). Downes score, RDS grades, and interleukin 8 (IL-8) levels were monitored and measured on the first and fifth days of incubation. RESULTS Statistically significant differences (SSDs) in RDS grades, Downes score, and IL-8 levels on the fifth day of admission were observed between groups 1 and 2 (p = 0.001) and between the first and fifth days of incubation in group 1 (p = 0.001). The SSDs in the duration of hospitalization (p = 0.001) and the number of neonates receiving mechanical ventilation (p = 0.032) were found between both groups. CONCLUSIONS Budesonide inhalation is associated with improvements in clinical and laboratory parameters in neonates with RDS. [ABSTRACT FROM AUTHOR]

The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m(3), respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days).

Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections.

James F Donohue,1 Donald A Mahler,2,3 Sanjay Sethi4 1Pulmonary Medicine, UNC School of Medicine, Chapel Hill, NC, USA; 2Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 3Director of Respiratory Services, Valley Regional Hospital, Claremont, NH, USA; 4University at Buffalo, State University of New York, Buffalo, NY, USACorrespondence: James F DonohueUNC School of Medicine, 4125 Bioinformatics Building CB#7020, Chapel Hill, NC 27599-0001, USATel +1 984-974-5703Fax +1 984-974-5737Email James_Donohue@med.unc.eduAbstract: Bronchodilation with muscarinic antagonists, β2-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using “duration and lung selectivity-by-design.” This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV1) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.Keywords: long-acting muscarinic antagonist, LAMA, bronchodilator, inhaled, once daily, nebulizer

Foreign body (FB) inhalation in children is a common and potentially life-threatening occurrence encountered in pediatric emergency medicine. A wide range of clinical presentations including often delayed onset of symptoms make it challenging to identify and provide a timely diagnosis. This increases the risk of complications and leads to suboptimal outcomes. For instance, inhalation of sharp objects may lead to perforations and migrations to surrounding structures making it difficult to retrieve the FB as seen in this case. Additionally, the onset of symptoms can vary, making it difficult to diagnose based on a patient's history alone. An unusual case of an inhaled sharp metallic object (dental bur) in a 13-year-old boy that migrated from the left lower thorax to the right perihilar and finally to the gastric lumen is presented a week after the incident. A 13-year-old boy presented to the emergency department with mild symptoms. He was stable with normal chest findings. Previous rigid bronchoscopy failed to localize and remove the FB and the thoracotomy. A post-operative X-ray was done, and the migration of the FB to the right middle lobe was revealed. A flexible bronchoscopy was then performed, again with no positive results. It was finally the abdominopelvic CT scan followed by the gastroduodenal esophagoscopy that allowed us to visualize and remove the FB from the gastric lumen.  In this case, we review the literature to emphasize the diagnostic challenges of FB inhalation in children, focusing on key diagnostic clues that assist clinicians in managing this condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Id El Haj et al.)

This paper presents a review of the nature, range, and incidences of background pathology findings in the respiratory tract of cynomolgus monkeys and rats. Data were collected from 81 inhalation studies and 133 non-inhalation studies evaluated at 3 geographically distinct contract research organization facilities. The inhalation studies were comprised of 44 different small molecule pharmaceuticals or chemicals which were also analyzed in order to understand the patterns of induced changes within the respiratory tract. The lung was the most frequently affected organ in both species, with increased alveolar macrophages being the most common background and test article–related finding. In the upper respiratory tract (URT), inflammatory cell infiltrates were the most common background findings in the nasal cavity in monkeys. Induced URT findings were more frequent in rats than monkeys, with squamous metaplasia in the larynx, and goblet cell hyperplasia in the nasal cavity being the most common. Overall, the data revealed a limited pattern of response to inhaled molecules in the respiratory tract, with background and test article–related findings often occurring in the same regions. It is hoped that these data will assist in the interpretation of findings in the respiratory tract induced by novel inhaled small molecule entities. [ABSTRACT FROM AUTHOR]

Background: Use of digital communication technology has shown potential to improve asthma adherence and outcomes. Few studies have looked at patient preference around mode of medication reminders used to improve and maintain asthma medication adherence. Objective: To determine if, in a population already receiving automated medication reminders, offering a choice for preferred mode of reminder (text, email, phone) would improve their adherence and asthma outcomes over a 1-year period. Methods: This was a pragmatic, randomized controlled trial conducted at Kaiser Permanente Colorado involving 7522 adult patients with persistent asthma. Study patients were randomized to receive usual care or their choice of medication reminder. Differences between the 2 groups in both medication adherence and asthma outcomes were then assessed over the following year. Results: Only 30% of those offered a choice of medication reminder modality responded by making a choice, with 52% preferring text messaging. There was less of a decrease in adherence rate over the 1-year period in those who made a choice regarding the mode of medication refill reminder. There was no difference in asthma outcomes between those who did make a choice compared with those who did not make a choice regarding the mode of medication refill reminder. Conclusion: In a patient population already receivingmedication reminders, offering a choice about what type of technology-enabled asthma medication reminder patients wanted did not improve outcomes but did enable a subgroup to better maintain their medication adherence. [ABSTRACT FROM AUTHOR]

Despite progress over the past 30 years, pulmonary arterial hypertension remains a condition with high morbidity and mortality. Pharmacological and technological advances have shifted the approach to treating pulmonary arterial hypertension. Recent developments revolve heavily around novel routes of drug administration and delivery. In 2009, inhaled treprostinil was approved followed by oral treprostinil in 2013 providing patients with more convenient routes of administration compared with the parenteral alternatives. We are on the cusp of having the first fully implantable infusion pump for continuous intravenous treprostinil delivery. In 2019, generic treprostinil was approved, making the medication much more affordable for patients. In this review, we discuss in detail the recent developments surrounding both traditional and novel treprostinil products. [ABSTRACT FROM AUTHOR]

Inhaled granulocyte/macrophage colony-stimulating factor (GM-CSF) shows promise as a therapeutic to treat viral and bacterial pneumonia, but no mouse model of inhaled GM-CSF has been described. We sought to 1) develop a mouse model of aerosolized recombinant mouse GM-CSF administration and 2) investigate the protection conferred by inhaled GM-CSF during influenza A virus (IAV) infection against secondary bacterial infection with pneumococcus. To assess lower respiratory tract delivery of aerosolized therapeutics, mice were exposed to aerosolized fluorescein (FITC)-labeled dextran noninvasively via an aerosolization tower or invasively using a rodent ventilator. The efficiency of delivery to the lower respiratory tracts of mice was 0.01% noninvasively compared with 0.3% invasively. The airway pharmacokinetics of inhaled GM-CSF fit a two-compartment model with a terminal phase half-life of 1.3 h. To test if lower respiratory tract levels were sufficient for biological effect, mice were infected intranasally with IAV, treated with aerosolized recombinant mouse GM-CSF, and then secondarily infected with Streptococcus pneumoniae. Inhaled GM-CSF conferred a significant survival benefit to mice against secondary challenge with S. pneumoniae (P < 0.05). Inhaled GM-CSF did not reduce airway or lung parenchymal bacterial growth but significantly reduced the incidence of S. pneumoniae bacteremia (P < 0.01). However, GM-CSF overexpression during influenza virus infection did not affect lung epithelial permeability to FITC-dextran ingress into the bloodstream. Therefore, the mechanism of protection conferred by inhaled GM-CSF appears to be locally mediated improved lung antibacterial resistance to systemic bacteremia during IAV infection. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroid (ICS) is a mainstay treatment for controlling asthma and preventing exacerbations in patients with persistent asthma. Many types of ICS drugs are used, either alone or in combination with other controller medications. Despite the widespread use of ICSs, asthma control remains suboptimal in many people with asthma. Suboptimal control leads to recurrent exacerbations, causes frequent ER visits and inpatient stays, and is due to multiple factors. One such factor is the inappropriate ICS choice for the patient. While many interventions targeting other factors exist, less attention is given to inappropriate ICS choice. Asthma is a heterogeneous disease with variable underlying inflammations and biomarkers. Up to 50% of people with asthma exhibit some degree of resistance or insensitivity to certain ICSs due to genetic variations in ICS metabolizing enzymes, leading to variable responses to ICSs. Yet, ICS choice, especially in the primary care setting, is often not tailored to the patient's characteristics. Instead, ICS choice is largely by trial and error and often dictated by insurance reimbursement, organizational prescribing policies, or cost, leading to a one-size-fits-all approach with many patients not achieving optimal control. There is a pressing need for a decision support tool that can predict an effective ICS at the point of care and guide providers to select the ICS that will most likely and quickly ease patient symptoms and improve asthma control. To date, no such tool exists. Predicting which patient will respond well to which ICS is the first step toward developing such a tool. However, no study has predicted ICS response, forming a gap. While the biologic heterogeneity of asthma is vast, few, if any, biomarkers and genotypes can be used to systematically profile all patients with asthma and predict ICS response. As endotyping or genotyping all patients is infeasible, readily available electronic health record data collected during clinical care offer a low-cost, reliable, and more holistic way to profile all patients. In this paper, we point out the need for developing a decision support tool to guide ICS selection and the gap in fulfilling the need. Then we outline an approach to close this gap via creating a machine learning model and applying causal inference to predict a patient's ICS response in the next year based on the patient's characteristics. The model uses electronic health record data to characterize all patients and extract patterns that could mirror endotype or genotype. This paper supplies a roadmap for future research, with the eventual goal of shifting asthma care from one-size-fits-all to personalized care, improve outcomes, and save health care resources., (©Flory L Nkoy, Bryan L Stone, Yue Zhang, Gang Luo. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 17.04.2024.)

The increasing prevalence of ventilator-associated pneumonia (VAP) due to either multidrug-resistant (MDR) organisms or infections with limited treatment options (i.e. susceptible to only aminoglycosides or colisitin) coupled with a dearth of new antimicrobials has led clinicians to pursue alternative management strategies including the use of inhaled antibiotics (IA). To review the evidence surrounding the use of IA in the treatment of VAP with a focus on establishing a path whereby adjunctive IA could become a standard therapy for the treatment of specific VAP patient populations. A meta-analysis performed by the 2016 IDSA/ATS Hospital-acquired Pneumonia Guideline Committee; a PubMed and clinicaltrials.gov search for subsequent trials of IA for the treatment of VAP. Based on a meta-analysis of nine studies (RR 1.29; 95% CI 1.13–1.47), the 2016 IDSA/ATS Hospital-acquired Pneumonia Guideline Committee recommended that adjunctive IA be used to treat VAP due to Gram-negative bacilli that are susceptible to only aminoglycosides or polymyxins. Two subsequent randomized trials of adjunctive IA for the treatment of mechanically ventilated patients with pneumonia failed to demonstrate a benefit. Despite these results, an updated meta-analysis (n = 11) including these two recent trials suggests a benefit of adjunctive IA for the treatment of VAP due to MDR and difficult-to-treat infections (RR 1.2; 95% CI 1.05–1.57). Patients with VAP and limited intravenous antibiotic options are the individuals most likely to benefit from adjunctive IA and should be the focus of future investigative studies. Although vibrating mesh nebulizers predominate in pharmaceutical company-sponsored trials, these devices have not been directly compared with the traditional jet nebulizers in terms of efficacy or safety. [ABSTRACT FROM AUTHOR]

Abstract Background Transient tachypnea of the newborn (TTN) is a self-limiting disease that results from a reduction in the rate of lung fluid clearance in neonates. A delay in lung fluid absorption in neonates disrupts the transition from intrauterine to extrauterine life. Use of beta-adrenergic antagonists, such as salbutamol, accelerates lung fluid clearance. The current study aimed to evaluate the effect of inhaled salbutamol on the clinical progression of TTN treatment. Methods In the current triple-blind clinical trial, a total of 148 inpatients diagnosed with TTN were randomly divided into 2 groups. The treatment group (n = 74) received inhaled salbutamol and the placebo group (n = 74) received inhaled normal saline. The drug administration was started 6 h after birth and continued in the case of continued respiratory distress and the need for oxygen as adjuvant therapy for up to 72 h maximum after the initiation of treatment. To evaluate the response to treatment with inhaled salbutamol, we assessed the respiratory rate (RR), heart rate (HR), fraction of inspired oxygen (FIO2) level, and O 2 saturation at intervals of 30 min as well as 1 h and 4 h after drug administration. The results were compared between the groups. Results The results of the current study indicated a significant difference between the treatment and placebo groups in the treatment duration, hospitalization duration, need for continuous positive airway pressure therapy (CPAP), and time of oral feeding initiation. In addition, no complication was observed during the treatment. It is noteworthy that, following the improvement of disease symptoms and reduction of hospitalization. This reduction may decrease the treatment costs and anxiety of parents, which was associated with proper mental and economic outcomes. Conclusion Although, in the current study, drug administration was continued for 72 h maximum, the prescription of at most 4 doses of salbutamol may have had maximum efficiency in the remediation process. To evaluate the therapeutic role of inhaled salbutamol, further studies are recommended. [ABSTRACT FROM AUTHOR]

Background: Gram-negative (G-ve) bacilli, particularly Pseudomonas aeruginosa and Acinetobacter baumannii, are important opportunistic multidrug-resistant (MDR) pathogens in hospitalized patients, contributing to their morbidity and mortality. These organisms may still keep their sensitivity to colistin and allowed its use for these selective therapeutic indications. Objectives: The aim of the present study is to evaluate and compare the effectiveness and safety of both combined intravenous (i.v.) colistin with aerosolized colistin versus i.v. colistin alone in nosocomial pneumonia due to MDR G-ve pathogens in critically ill patients. Methods: 40 Patients were hospitalized in ICU due to different etiologies. These patients experienced nosocomial pneumonia. The pathogenic organisms were G-ve MDR bacilli and only susceptible to colistin. The first group received both i.v. colistin with aerosolized colistin versus (vs.) the second group who received i.v. colistin alone. Results: Mortality was less in patients who received i.v. plus inhaled colistin. Conclusion: Colistin is a reasonable safe last-line therapeutic alternative for pneumonia due to MDR G-ve pathogens. Aerosolized colistin may be considered as a useful adjunctive to i.v. colistin.

Foreign body in the nasal cavity is one of the most common paediatric otolaryngology emergencies and needs to be promptly addressed. The incidence of nasal foreign body getting dislodged secondary to unsuccessful attempts to take it out is quite high and can be potentially dangerous as it might cause fatal airway compromise. The chances of it getting impacted and retained in the nasopharynx are practical, although such cases are seldom encountered for primarily nasal foreign bodies. Nevertheless, the nasopharynx should always be looked for as a site of impaction of hidden foreign objects. Presence of enlarged adenoids could be of help as it may prevent accidental lodgement of displaced foreign body in the airway, but might also result in difficulty in locating and retrieving the foreign body because it acts as an anchor-pad with its grooves and crevasses. This report presents a rare, interesting case of a child with enlarged adenoids anchoring a metallic ring and describes the clinical presentations and relevant management of a nasal foreign body dislodged and lost in the nasopharynx.

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation. [ABSTRACT FROM AUTHOR]

Background: Ventilator-associated respiratory infections (tracheobronchitis, pneumonia) contribute significant morbidity and mortality to adults receiving care in intensive care units (ICU). Administration of broad-spectrum intravenous antibiotics, the current standard of care, may have systemic adverse effects. The efficacy of aerosolized antibiotics for treatment of ventilator-associated respiratory infections remains unclear. Our objective was to conduct a systematic review of the efficacy of aerosolized antibiotics in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT), using the Cochrane Collaboration guidelines.Methods: We conducted a search of three databases (PubMed, Web of Knowledge and the Cochrane Collaboration) for randomized, controlled trials studying the use of nebulized antibiotics in VAP and VAT that measured clinical cure (e.g., change in Clinical Pulmonary Infection Score) as an outcome measurement. We augmented the electronic searches with hand searches of the references for any narrative review articles as well as any article included in the systematic review. Included studies were examined for risk of bias using the Cochrane Handbook's "Risk of Bias" assessment tool.Results: Six studies met full inclusion criteria. For the systemic review's primary outcome (clinical cure), two studies found clinically and statistically significant improvements in measures of VAP cure while four found no statistically significant difference in measurements of cure. No studies found inferiority of aerosolized antibiotics. The included studies had various degrees of biases, particularly in the performance and detection bias domains. Given that outcome measures of clinical cure were not uniform, we were unable to conduct a meta-analysis.Conclusions: There is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT. Additional, better-powered randomized-controlled trials are needed to assess the efficacy of inhaled antibiotic therapy for VAP and VAT. [ABSTRACT FROM AUTHOR]

Glucocorticosteroids are a group of structurally related molecules that includes natural hormones and synthetic drugs with a wide range of anti-inflammatory potencies. For synthetic corticosteroid analogues it is commonly assumed that the therapeutic index cannot be improved by increasing their glucocorticoid receptor binding affinity. The validity of this assumption, particularly for inhaled corticosteroids, has not been fully explored. Inhaled corticosteroids exert their anti-inflammatory activity locally in the airways, and hence this can be dissociated from their potential to cause systemic adverse effects. The molecular structural features that increase glucocorticoid receptor binding affinity and selectivity drive topical anti-inflammatory activity. However, in addition, these structural modifications also result in physicochemical and pharmacokinetic changes that can enhance targeting to the airways and reduce systemic exposure. As a consequence, potency and therapeutic index can be correlated. However, this consideration is not reflected in asthma treatment guidelines that classify inhaled corticosteroid formulations as low-, mid- and high dose, and imbed a simple dose equivalence approach where potency is not considered to affect the therapeutic index. This article describes the relationship between potency and therapeutic index, and concludes that higher potency can potentially improve the therapeutic index. Therefore, both efficacy and safety should be considered when classifying inhaled corticosteroid regimens in terms of dose equivalence. The historical approach to dose equivalence in asthma treatment guidelines is not appropriate for the wider range of molecules, potencies and device/formulations now available. A more robust method is needed that incorporates pharmacological principles. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disorder characterized by relative or absolute deficiency of insulin, resulting in hyperglycemia. The main treatment of diabetes relies on subcutaneous insulin administration by injection or continuous infusion to control glucose levels, besides oral hypoglycemic agents for type 2 diabetes. Novel routes of insulin administration are an area of research in the diabetes field as insulin injection therapy is burdensome and painful for many patients. Inhalational insulin is a potential alternative to subcutaneous insulin in the management of diabetes. The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium facilitates systemic delivery of insulin via pulmonary administration. Inhaled insulin has been recently approved by Food and Drug Administration (FDA). It is a novel, rapid-acting inhaled insulin with a pharmacokinetic profile that is different from all other insulin products and comparatively safer than the previous failed inhaled insulin (Exubera). [ABSTRACT FROM AUTHOR]

Background The link between asthma and inhaled workplace exposures has been long appreciated, and yet aggravation of asthma symptoms by work conditions, known as work-aggravated asthma (WAA), remains relatively common. Sources of data A review of the literature published over the last 3 years was carried out, and additional key articles were included from outside this timeframe. Agreement WAA is commonly reported by workers with asthma. One published assessment of 12 studies identified a median prevalence of 21.5% among workers with asthma. Commonly reported causes included a variety of inhaled dusts, smoke, vapours, fumes, gases and mists, common and workplace-specific aeroallergens, physical environmental factors including temperature and humidity and physical activity at work. Controversy Remains in relation to definition, and how to distinguish WAA from occupational asthma in which there is sensitization to an agent in the workplace. Both these areas, and the development of workplace interventions to reduce WAA, are timely topics for future research. [ABSTRACT FROM PUBLISHER]

Melioidosis is a tropical disease caused by ingestion, percutaneous inoculation or inhalation of the Gram-negative soil saprophyte Burkholderia pseudomallei. We developed a reproducible experimental murine model of pneumonic melioidosis induced by inhalation of aerosolized B. pseudomallei 1026b. In a series of experiments performed to bracket the lethal dose, we found that C57 BL/6 mice were modestly more resistant than BALB/c mice (median lethal dose 334 CFU/lung vs 204 CFU/lung). We further characterized infection and pulmonary inflammation in C57 BL/6 mice infected with a sublethal dose. We observed pulmonary replication and dissemination of bacteria to distant organs in the first days after infection, followed by bacterial containment by day 4 and no evidence of recrudescent infection for up to 2 months. We measured a robust host inflammatory response notable for a neutrophilic bronchoalveolar lavage fluid profile, elevated cytokines and chemokines in the lung and serum and scattered foci of neutrophilic infiltrates in the alveoli and in a perivascular distribution on histological analysis. We previously noted a similar pattern of inflammation in mice infected with aerosolized B. thailandensis. This report builds on the limited literature describing experimental murine pneumonic melioidosis induced by aerosol and characterizes pulmonary infection and resultant inflammation in C57 BL/6 mice infected with aerosolized B. pseudomallei. This model has utility for the study of bacterial and host factors that contribute to the virulence of melioidosis. [ABSTRACT FROM AUTHOR]

The article presents a meta-analysis that investigates the efficacy of intranasal corticosteriods in treating acute sinusitis in England. Researchers studied 2,495 patients who took corticosteriods and antibiotics. They found that intranasal corticosteriod offers small therapeutic benefits to patients with acute sinusitis.

Respiratory type-IV hypersensitivity reactions due to corticosteroids is a rare phenomenon. We describe two such cases. The first is a 37- year-old atopic woman who developed labial angioedema and nasal itching after the use of budesonide nasal spray. A month later, after the first puffs of a formoterol/budesonide spray prescribed for asthma, she noticed symptoms of tongue and oropharyngeal itching and redness with subsequent dysphagia, labial and tongue angioedema, and facial oedema. The second is a 15-year-old non-atopic woman who reported pruritic eruptions around the nostrils after using a budesonide nasal spray. A year later she presented with nasal pruritus with intense congestion and labial and facial oedema after using the same spray. Both patients were evaluated with patch-tests using the commercial T.R.U.E. test®, a budesonide solution, and corticosteroid creams. Test evaluation was performed at 48 and 96 hours. In both patients, patch tests were positive to budesonide (++) on the second day. The first patient also had a positive (+) reaction to tixocortol-21-pivalate. All the other patch tests were negative. Clinicians should be aware that hypersensitivity reactions may occur during the use of nasal or inhaled corticosteroids. [ABSTRACT FROM AUTHOR]

Summary: Background: Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens. Methods: To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin. Results: Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (±SD) daily dosage of aerosolized colistin was 2.2 (±0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%. Conclusions: Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety. [Copyright &y& Elsevier]

Summary: Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammatory process in the large and small airways, as well as in the lung parenchyma. Although the role of oral corticosteroids in the management of acute exacerbations of COPD is well documented, its role in stable COPD is not clear. We examined the anti-inflammatory effect of inhaled budesonide on the percentage of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL) and their correlation with spirometry and symptom scores. Twenty-six patients with stable COPD were randomised, in a double-blinded, placebo-controlled trial with either 800μg of inhaled budesonide or placebo for a 6-month period. The budesonide-treated subjects had significant reductions in IL-8 levels in the BAL after therapy (mean±sem, 1.53±0.72 at baseline vs. 0.70±0.48ng/ml at 6 months, ) and a reduction in the mean percentages of neutrophils (17.16±2.67% vs. 13.25±2.28% ). The improvement in sputum production was of borderline () significance but there was no improvement in lung function. In stable patients with COPD, treatment with inhaled budesonide for a period of 6 months has a positive effect on markers of lung inflammation, as assessed by reduction in percentage neutrophils and IL-8 concentration in BAL. [Copyright &y& Elsevier]

Vestergaard P, Rejnmark L, Mosekilde L (Aarhus University Hospital, Aarhus, Denmark). Fracture risk associated with systemic and topical corticosteroids.J Intern Med2005;257: 374–384.To study the fracture risk associated with the use of corticosteroids in any formulation and administration.Case–control study.Community-based study in Denmark.Cases were all subjects with any fracture sustained during the year 2000 (n = 124 655). For each case, three controls (n = 373 962) matched on age and gender were randomly drawn from the background population. Adjustments were made for concurrent diseases (lung diseases, rheumatic disorders), use of other drugs (inhaled bronchodilators), contacts to hospitals and general practitioners, and social variables.An increased risk of any fracture, hip, spine, and forearm fractures was present with use of more than 2.5 mg of prednisolone or equivalent orally per day. For inhaled corticosteroids a limited increase in the risk of any fracture was present in users of more than 7.5 mg prednisolone equivalents per day (equivalent to 1875 μg of budesonide per day). However, no increase in the risk of hip, spine or forearm fractures was present in users of inhaled corticosteroids. For other topical corticosteroids (dermal, rectal, nasal, local application in the mouth, the eyes or the ears) no increase in fracture risk could be demonstrated even at high doses after adjustment for confounders.Ingestion of more than 2.5 mg of oral prednisolone equivalents per day is associated with an increase in fracture risk. No increase is associated with inhaled corticosteroids except at daily dosages above 7.5 mg of prednisolone equivalents. No increase in fracture risk is associated with other forms of topical corticosteroids. [ABSTRACT FROM AUTHOR]

Aims To assess the absolute bioavailability, pharmacokinetics and metabolism of beclomethasone dipropionate (BDP) in man following intravenous, oral, intranasal and inhaled administration. Methods Twelve healthy subjects participated in this seven-way cross-over study where BDP was administered via the following routes: intravenous infusion (1000 µg), oral (4000 µg, aqueous suspension), intranasal (1344 µg, aqueous nasal spray) and inhaled (1000 µg ex-valve, metered dose inhaler). The contribution of the lung, nose and gut to the systemic exposure was assessed by repeating the inhaled, intranasal and oral dosing arms together with activated charcoal, to block oral absorption. Blood samples were collected for 24 h postdose for the measurement of BDP, beclomethasone-17-monopropionate (B-17-MP) and beclomethasone (BOH) in plasma by liquid chromatography tandem mass spectrometry. Results Intravenous administration of BDP (mean CL 150 l h-1, Vss 20 l, t½ 0.5 h) was associated with rapid conversion to B-17-MP which was eliminated more slowly (t1/2 2.7 h). In estimating the parameters for B-17-MP (mean CL 120 l h-1, Vss 424 l) complete conversion of BDP to B-17-MP was assumed. The resultant plasma concentrations of BOH were low and transient. BDP was not detected in plasma following oral or intranasal dosing. The mean absolute bioavailability (%F, 90% CI; nominal doses) of inhaled BDP was 2% (1–4%) and not reduced by coadministration of charcoal. The mean percentage F of the active metabolite B-17-MP was 41% (31–54%), 44% (34–58%) and 62% (47–82%) for oral, intranasal and inhaled dosing without charcoal, respectively. The corresponding estimates of nasal and lung absorption, based on the coadministration of charcoal, were < 1% and 36% (27–47%), respectively. Conclusions Unchanged BDP has negligible oral and intranasal bioavailability with limited absorption following inhaled dosing due to extensive (95%) presystemic conversion of BDP to B-17-MP in the lung. The oral and intranasal bioavailabilities of the active metabolite B-17-MP were high and similar, but direct absorption in the nose was insignificant. The total inhaled bioavailability of B-17-MP (lung + oral) was also high (62%) and approximately 36% of this was due to pulmonary absorption. Estimates of oral bioavailability and pulmonary deposition based on total BOH were approximately half those found for B-17-MP. [ABSTRACT FROM AUTHOR]