The pulmonary microvasculature plays an essential role in maintaining alveolar integrity, but the direct effects of inhaled corticosteroids (ICS) on pulmonary endothelial cell function remain poorly understood. We investigated the effects of budesonide, formoterol, and their combination on endothelial network formation, apoptosis, migration, proliferation, and efferocytosis using human pulmonary microvascular endothelial cells (HPMEC-ST1.6R), A549 alveolar epithelial cells, and phagocytic cell models. Budesonide, alone or combined with formoterol, altered endothelial network formation on Matrigel by reducing total tubule length and the number of junctions while increasing tubule thickness, indicating reduced branching complexity. Budesonide also decreased epithelial secretion of the pro-angiogenic mediators VEGF, IL-8, and MCP-1. An independent set of experiments showed that fluticasone propionate similarly reduced VEGF, IL-8, MCP-1, TNF-α, and IL-6, supporting a class effect of corticosteroids on the epithelial secretome. Despite reducing angiogenic responses, budesonide protected endothelial cells from apoptosis, reduced caspase-3/7 activity, accelerated wound closure without affecting proliferation, preserved endothelial spheroid integrity, and enhanced efferocytosis. Formoterol alone had minimal effects and did not consistently enhance budesonide responses. Together, these in vitro findings suggest that, in the cell models studied, pulmonary endothelial responses to the ICS/LABA combinations tested are determined predominantly by the corticosteroid component, which suppresses pro-angiogenic mediator secretion while preserving endothelial survival and repair. As an exploratory cell-based study, these observations are hypothesis-generating and require confirmation in primary cells and in vivo models before clinical inferences can be drawn.

Manufacturers are adopting propellants for use in pressurized metered-dose inhalers (pMDIs) that have lower global warming potentials (GWPs) than the propellants traditionally used in pMDIs. Hydrofluoroalkane (HFA)-134a has been used as the propellant in the pMDI used to deliver the fixed-dose triple combination of budesonide, glycopyrrolate, and formoterol fumarate (BGF); following successful clinical evaluation, the BGF pMDI is now being transitioned to the next generation propellant hydrofluoroolefin (HFO)-1234ze(E), which has near-zero GWP. We describe formulation development efforts that led to the selection of HFO-1234ze(E) over another propellant, HFA-152a, for reformulation. Propellant-specific studies evaluated active pharmaceutical ingredient (API) stability and aerodynamic particle size distribution (aPSD). Those analyses have been complemented by in silico regional lung deposition modeling conducted after the clinical evaluation of the reformulated BGF pMDI. HFO-1234ze(E) supported favorable stability and aPSD characteristics for BGF pMDI reformulation, compared with HFA-152a, and modeling predicted regional deposition consistent with therapeutic intent. Given that each pMDI is a unique combination of APIs, device, propellant, and excipients, propellant substitution requires product-specific evidence and regulatory approval, and typically takes several years. Targeted analyses, such as those described here, helped to identify the most suitable candidate propellant for successful substitution in the BGF pMDI.

Chronic cough in patients with systemic lupus erythematosus can be difficult to evaluate, especially when initial testing is unrevealing. We report the case of a 33-year-old woman with long-standing systemic lupus erythematosus, biopsy-proven lupus nephritis, prior extrapulmonary pericardial tuberculosis, and no active or passive smoking exposure who developed a persistent dry cough for six months. She was initially treated for gastroesophageal reflux disease with pantoprazole, without meaningful relief. Chest radiography and swallowing assessment were normal. Initial pulmonary function testing in July 2023 was formally interpreted as moderate obstructive airways disease, mild parenchymal restriction, and a moderately severe diffusion defect, without a significant bronchodilator response. High-resolution volumetric computed tomography of the chest with dynamic airway assessment showed no emphysema, bronchiectasis, interstitial lung disease, tracheomalacia, or acute cardiopulmonary process. Her cough improved substantially after inhaled therapy with albuterol and budesonide/glycopyrrolate/formoterol fumarate. Repeat pulmonary function testing in October 2023 showed improved spirometric values, but the forced expiratory volume in one second/forced vital capacity ratio remained preserved, and hemoglobin-adjusted diffusing capacity remained reduced at 64% predicted. This case highlights a diagnostic pitfall: inhaler-responsive chronic cough and a pulmonary function report suggesting obstruction should be evaluated together with post-bronchodilator spirometry, diffusing capacity, imaging, and exposure history. In systemic lupus erythematosus, a persistent cough may be associated with clinically relevant pulmonary function abnormalities even when chest imaging is unrevealing.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease associated with inflammation and obstruction of the airways. COPD progresses through 4 stages of increasing airflow limitation — mild, moderate, severe, and very severe — with symptoms and functional limitations worsening at each stage. Symptoms include difficulty in breathing, cough, and flare-ups (exacerbations) that may require hospitalization. As of 2022–2023, the prevalence of COPD was 8.74% in Canada.

A sensitive spectrofluorimetric technique exhibiting acceptable selectivity was established for the quantification of formoterol (FMT) via the von Pechmann condensation reaction, leading to the formation of intensely fluorescent coumarin derivatives. In this reaction, FMT interacts with ethyl acetoacetate in the presence of concentrated sulfuric acid, producing a fluorescent product. The emitted fluorescence was recorded at 445 nm following excitation at 361 nm. Experimental parameters influencing the reaction were carefully optimized to achieve maximum fluorescence response and method stability. The proposed method exhibited excellent linearity across the concentration range of 20-500 ng mL[-1], with a correlation coefficient (r) of 0.9998. The limits of detection (LOD) and quantification (LOQ) were found to be 4 ng mL[-1] and 12 ng mL[-1], respectively. Acceptable selectivity was demonstrated under the studied formulation conditions, as no significant interference was observed from commonly used pharmaceutical excipients, including lactose monohydrate, magnesium stearate, gelatin, titanium dioxide and placebo. A reaction pathway based on the reported von Pechmann condensation was proposed, and the method was validated in accordance with ICH guidelines. The applicability of the method was successfully demonstrated for the determination of FMT in pharmaceutical dosage forms, including content uniformity testing, showing satisfactory recovery results. Finally, the environmental impact of the method was assessed using various greenness evaluation tools, indicating a favorable greenness profile and practical applicability.

Asthma treatment has long relied on short-acting β2-adrenergic receptor (β2-AR) agonists (SABA) such as salbutamol for as-needed relief, often without concurrent anti-inflammatory therapy. Emerging data link frequent SABA use to higher exacerbation rates and mortality. Current recommendations organize asthma treatment into Track 1, with as-needed inhaled corticosteroid (ICS)/formoterol used also as maintenance-and-reliever therapy, and Track 2, with SABA or ICS/SABA reliever plus separate maintenance; Track 1 is identified as the preferred option.