Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

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.

A 53-year-old Black woman was referred to the pulmonary clinic for progressively worsening exertional dyspnea over the past 3 years and a chronic nonproductive cough. She had a history of childhood asthma, with 2 prior hospitalizations, as well as an unspecified nasal surgery 20 years ago. She was diagnosed with bronchiectasis 10 years ago by her primary care physician and was compliant with airway clearance techniques, including nebulized hypertonic (7%) saline and albuterol-ipratropium and a positive expiratory pressure handheld device. Review of systems was positive for fatigue, seasonal allergies, occasional heartburn, and occasional stiffness of the small joints of the hands. She had a family history of asthma in her cousin and sarcoidosis in her father; her mother had a significant smoking history and was deceased from complications of lung cancer. She had no history of occupational exposures, no pets, and no significant travel history.

Enantiomeric separation is essential in pharmaceutical analysis because enantiomers can differ markedly in pharmacological activity, metabolism, and safety. HPLC using chiral mobile-phase additives (CMPAs), particularly cyclodextrin-based selectors, provides a flexible and cost-effective alternative to dedicated chiral stationary phases. However, conventional cyclodextrin CMPA systems are often limited by insufficient stereodiscrimination under aqueous-organic mobile-phase conditions, where solvation and weak noncovalent interactions can restrict chiral recognition. This study explores the potential of deep eutectic solvents (DESs) as auxiliary mobile-phase modifiers for enhancing enantioseparation in β-cyclodextrin polymer-based HPLC chiral mobile phase analysis.

Functionalized imine-linked covalent organic polymers (COPs) have attracted tremendous attention as adsorbent. At present, most imine-linked COPs are functionalized relying on benzene groups, limiting sufficient flexibility for grafting diverse functional groups. Herein, Ugi reaction is employed to flexibly anchor carboxylic acids and isonitriles with diverse molecular structures onto the imine bonds of COP skeletons. Considering that four illegal food additives, salbutamol, ractopamine, terbutaline and ribavirin, can specifically bind with boric acid, this work selects 4-carboxyphenylboronic acid and tert‑butyl isocyanate, yielding a boronate affinity imine-linked COP. The adsorption performance of the obtained adsorbent is investigated in detail. The as-prepared adsorbent exhibits excellent selectivity, and high adsorption capacities ranging from 119.6 to 385.3 μmol/g towards four analytes. Moreover, the developed dispersive solid-phase extraction (DSPE) combined with HPLC gives low limits of detection (0.21-0.38 μg/kg) and wide linear ranges (1.2-300.0 μg/kg) for the four targets in feed samples. These results confirm the excellent adsorption properties of the adsorbent and verify the feasibility of Ugi reaction for post-synthetic functionalization of COPs.

Tracheomalacia (TM), the most common abnormality of the pediatric trachea, results in dynamic expiratory airway collapse due to weakened cartilage and reduced smooth muscle tone. Although bronchodilators such as albuterol are widely used in children with wheezing, their impact on TM remains unclear, because prior studies have not simultaneously evaluated tracheal and lung mechanics in vivo. This study aimed to separately quantify the effects of albuterol on both tracheal distensibility and compliance, as well as lung compliance, using a controlled porcine model. Ten spontaneously breathing swine underwent high-resolution computed tomography (CT) imaging at multiple controlled tracheal lumen pressures (PLUM) ranging from +10 to -10 cmH2O, both before and after administration of 5 mg nebulized albuterol. Tracheal and pleural pressures were simultaneously recorded. Three-dimensional airways and lungs were segmented from CT images to calculate cross-sectional areas and volumes. Tracheal distensibility and compliance, as well as lung compliance, were determined by the slope of area or volume versus transmural pressure. Albuterol significantly increased tracheal distensibility (4.30 ± 1.0 to 4.78 ± 1.3 mm[[2]]/mmHg, p=0.010) and tracheal compliance (327 ± 102 to 367 ± 117 mm[[3]]/mmHg, p=0.018). Lung compliance also increased significantly in 9 evaluable swine ((2.9 ± 1)×10[[4]] to (3.8 ± 1.1)×10[[4]] mm[[3]]/mmHg, p=0.010). Albuterol increases both tracheal and lung compliance, supporting clinical concerns that bronchodilators may exacerbate airway collapse in TM. These findings demonstrate the complex and competing mechanical effects of bronchodilators in TM and stress the importance of accounting for both tracheal and lung responses in managing dynamic airway collapse.

Prostate, bladder, and corpus cavernosum share common pathophysiological mechanisms involving smooth muscle tone regulation through cyclic nucleotide signaling, particularly cAMP and cGMP pathways. Probenecid, a classical uricosuric agent, has emerged as a candidate for drug repurposing due to its ability to inhibit multidrug resistance-associated proteins 4/5 (MRP4/MRP5), which mediate the cellular efflux of cyclic nucleotides, as well as pannexin-1 channels, organic anion transporters, TRPV2 channels, and purinergic receptors. Given that lower urinary tract symptoms, benign prostatic hyperplasia, and erectile dysfunction frequently coexist and share overlapping signaling pathways, we hypothesized that probenecid could potentiate smooth muscle relaxation mediated by cAMP- or cGMP-elevating agents across these tissues. Using isolated rat bladder, prostate, and corpus cavernosum, we evaluated the functional effects of probenecid (0.1-1 mM) through concentration-response curves and intracellular cyclic nucleotide quantification. Probenecid potentiated relaxation induced by β-adrenoceptor agonists and adenosine in the bladder, accompanied by increased intracellular cAMP without changes in cGMP. In prostate, probenecid enhanced relaxation induced by cAMP- and cGMP-elevating agents and increased intracellular cAMP when combined with salbutamol. In corpus cavernosum, probenecid induced relaxation per se and potentiated responses to acetylcholine, sodium nitroprusside, phosphodiesterase inhibitors, and β-agonists, with concurrent increases in both cAMP and cGMP. Selective tools targeting OAT1/3, P2X7 receptor and TRPV2 channels did not replicate these effects, whereas pannexin-1 inhibition potentiated acetylcholine-induced relaxation only in the corpus cavernosum. In conclusion, probenecid modulates smooth muscle relaxation across urogenital tissues and may represent a potential adjunct in the treatment of lower urinary tract symptoms and erectile dysfunction.

Background: Supplemental oxygen and aerosol therapy may be used simultaneously to treat neonates suffering from hypoxemia caused by respiratory diseases. Due to the cost and lack of availability of oxygen cylinders in some countries, oxygen concentrators are a reported substitute. We assessed whether an oxygen concentrator compared to low-flow oxygen therapy impacts neonatal aerosol drug delivery. Methods: A vibrating mesh nebulizer (A-VMN; Aerogen Solo) was used to aerosolize a 500 µg dose of salbutamol. The aerosol was delivered via a nasal cannula to a neonate head model in combination with oxygen concentrator at gas flow rates of 0.2, 1.0, and 5.0 L per minute (LPM), and low-flow oxygen therapy at gas flow rates of 1.0, 4.0, and 5.0 LPM. Emitted and tracheal doses were recorded. The impact of A-VMN operation and refill on circuit pressure in both systems was also measured. Results: The oxygen concentrator delivered a higher emitted dose than the low-flow system, the largest emitted dose (%) being 20.58 ± 0.50% and 14.69 ± 0.89%, respectively, at 1.0 LPM, p = 0.018. At 5.0 LPM, the tracheal dose was 11.01 ± 0.29% for the oxygen concentrator compared to 9.66 ± 1.53% for low-flow oxygen therapy, p = 0.073. Refill and operation of the A-VMN did not impact the circuit pressure in either system. Conclusions: This study shows that the system used to provide concurrent aerosol and supplemental oxygen therapy has a significant impact on the quantity of nebulized drug delivered to patients.