Search Results (627)

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Vilobelimab, a first-in-class, human–mouse chimeric immunoglobulin G4 (IgG4) kappa monoclonal antibody, targets human complement component 5a (C5a) in plasma. Unlike upstream complement inhibitors, vilobelimab does not inhibit the generation of the membrane attack complex (C5b-9), necessary to mitigate certain infections. C5a is a strong anaphylatoxin and chemotactic agent that plays an essential role in both innate and adaptive immunity. Elevated levels of C5a have been associated with pathologic processes, including sepsis and inflammatory respiratory disorders such as acute respiratory distress syndrome (ARDS). Blocking C5a with vilobelimab has shown therapeutic promise. A randomized, multicenter placebo-controlled Phase III study of vilobelimab in patients with severe COVID-19 (PANAMO) found that patients treated with vilobelimab had a significantly lower risk of death by day 28 and 60. Based on this study, the United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Gohibic^® (vilobelimab) injection for the treatment of COVID-19 in hospitalized adults when initiated within 48 h of receiving invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). In January 2025, the European Commission (EC) granted marketing authorization for Gohibic^® (vilobelimab) for the treatment of adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ARDS who are receiving systemic corticosteroids as part of standard of care and receiving IMV with or without ECMO. Herein, we review the mechanism of action of vilobelimab in selectively inhibiting C5a-induced inflammation, outlining its bench-to-bedside development from the fundamental biology of the complement system and preclinical evidence through to the clinical data demonstrating its life-saving potential in the management of COVID-19–induced ARDS. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, synovial inflammation, and abnormal bone remodeling. Current therapies, such as NSAIDs, corticosteroids, and hyaluronic acid injections, primarily alleviate symptoms but often cause systemic side effects and fail to modify disease progression. Novel drug delivery systems (NDDS), including liposomes, polymer microspheres, nanoparticles, hydrogels, and biomimetic carriers, have emerged to enhance drug targeting, prolong retention, and reduce toxicity. These systems enable controlled release of anti-inflammatory, antioxidant, and gene therapies, improving therapeutic outcomes. However, challenges remain in biocompatibility, scalability, and clinical translation. Future efforts should focus on optimizing material design, functionality, and personalized approaches to facilitate the clinical application of NDDS for OA treatment. Full article

Background/Objectives: The post-COVID-19 condition frequently includes dysphonia. We aimed to assess objective and subjective voice disorders and short-term responses to multimodal therapy in patients with isolated post-COVID-19 dysphonia. Methods: This retrospective, single-center pre–post study screened 244 post-COVID-19 patients; a subset of 14 with isolated dysphonia underwent standardized assessment at baseline and at 1-month follow-up. Patient-reported outcomes (Voice Handicap Index, VHI; Voice-Related Quality of Life, V-RQOL) and endoscopic evaluation were performed using videolaryngostroboscopy (LVS) and high-speed videoendoscopy (HSV) with kymographic analysis to quantify parameters describing vocal fold oscillations. The treatment included short-term systemic corticosteroids, inhaled corticosteroids, hyaluronic-acid inhalations, and structured voice therapy. Results: At baseline, HSV revealed signs of glottal insufficiency—irregular and asymmetric vocal fold motion, reduced amplitude and pliability, a disrupted mucosal wave, and an increased open quotient. At follow-up, HSV showed increased oscillation, amplitude, and cycle regularity with reduced left–right asymmetry and phase differences; phonovibrograms displayed clearer and more structured patterns. Perturbation indices decreased across jitter and shimmer measures, and the mean fundamental frequency was lower. Improvements in instrumental measures aligned with better VHI and V-RQOL scores. Conclusions: In patients with persistent dysphonia after acute SARS-CoV-2 infection, comprehensive ENT evaluation with instrumental laryngeal assessment is warranted. Short-term multimodal management was associated with improvements in both HSV-derived measures and patient-reported outcomes; confirmation in controlled studies is needed. Full article

Endocrine axes are pathways of interactions involved in various aspects of the organism’s functioning, also implicated in deviations from physiological states leading to pathological conditions. The hypothalamic–pituitary–adrenal (HPA) axis releases corticosteroid hormones promoting adaptation to environmental stimuli (acute stress) or inducing altered conditions due to long-term noxious solicitations (chronic stress). The HP–gonadal (HPG) axis regulates reproductive activities by releasing gonadal steroids. These axes have been shown to engage in reciprocal inhibition under certain conditions, particularly when they rise beyond normal ultradian and circadian fluctuations. Based on the literature data, we reconstructed a neuroendocrine network responsible for this type of interaction. Thereafter, we developed a model of the HPA-HPG inhibition based on a series of nonlinear interactions represented by a system of differential equations in the Matlab environment. The quantitative analysis of the system’s behavior revealed the occurrence of bifurcations leading to bistable behavior, allowing us to detect bifurcation parameters. Bifurcation arises as the system’s components increase hypersensitivity and sustained activity in response to activating inputs. This involves transition from a single low-activity attractor to two distinct attractors, with a new high-activity state representing a breakdown of homeostasis. These results provide insights into the potential involvement of the HPA-HPG interaction in neuroendocrine disorders, and the identification of therapeutic targets from bifurcation parameters. Full article

Background/Objectives: The aim of this study was to determine the suspected adverse drug reaction (ADR) profile of leukotriene receptor antagonists (LTRAs; montelukast and zafirlukast) relative to first-line asthma medications such as short-acting beta agonists (SABAs; salbutamol) and inhaled corticosteroid (ICS; beclomethasone) in the United Kingdom. to determine the chemical and pharmacological rationale for the suspected ADR signals. Methods: Properties of the asthma medications (pharmacokinetics and pharmacology) were datamined from the chemical database of bioactive molecules with drug-like properties, the European Molecular Biology Laboratory (ChEMBL). Suspected ADR profiles of the asthma medications were curated from the Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card interactive Drug Analysis Profiles (iDAP) and concatenated to the standardised prescribing levels (using Open Prescribing data) between 2018 and 2023. Results: Total ADRs per 100,000 R_x (p < 0.001) and psychiatric system organ class (SOC) ADRs (p < 0.001) reached statistical significance. Montelukast exhibited the greatest ADR rate at 15.64 per 100,000 R_x. Conclusions: Relative to the controls, montelukast displays a range of suspected system organ class level ADRs. For the credible and previously reported psychiatric ADRs, montelukast is statistically significant (p < 0.001). A mechanistic hypothesis is proposed based on polypharmacological interactions in combination with cerebrospinal fluid (CSF) levels attained. Montelukast had the highest nervous disorder ADR rate at 1.71 per 100,000 R_x, whereas beclomethasone and salbutamol had lower rates (0.43 and 0.14, respectively). These ADRs share a similar background to psychiatric ADRs with CSF penetrability involved and affecting the dopamine axis. This work further supports the monitoring of montelukast for rare but important neuropsychiatric side effects. Full article

Cortisol follows a 24 h circadian rhythm that plays a pivotal role in maintaining the optimal function of various physiological systems in alignment with behavioural cycles. Its synthesis and secretion are regulated by the hypothalamic–pituitary–adrenal (HPA) axis. The 24 h fluctuations of cortisol may result from physiological changes influencing its regulation, or conversely, hormone-mediating physiological changes within the body. This review mainly aims to synthesize current evidence on methods for detecting cortisol. In addition, it focuses on evaluating cortisol’s potential as a biomarker for circadian disruption and related health impacts. A literature search was conducted across databases, including Google Scholar, PubMed, and Scopus, using search terms such as “circadian rhythm OR circadian clock OR circadian disruption OR circadian dysregulation” and “cortisol OR hydrocort* OR corticoid OR corticosteroid”. A total of 47 articles were included on methods of cortisol detection, and 41 articles were reviewed for their health implications. Cortisol measured via saliva, blood serum, urine, interstitial fluid (ISF), and sweat has been reported as suitable for 24 h monitoring, reflecting circadian regulation. In contrast, hair cortisol is suitable for identifying chronic changes and prolonged elevations in cortisol levels. This review highlights the stability, suitability, and challenges of each detection method, including reported cortisol levels across studies. Additionally, it provides a comprehensive overview of health implications associated with changes in cortisol, offering insights into its potential as a marker for circadian disruption and related health outcomes. Full article

Introduction: Evidence on steroid treatment for established bronchopulmonary dysplasia (BPD) is sparse. To our knowledge, a systematic review has never been conducted on this topic. This meta-analysis aims to synthesize available evidence for the use of postnatal steroids to treat established BPD. Methods: MEDLINE, Embase, Cochrane databases, and gray literature sources were searched without time or language restrictions until October 2024. We included randomized and non-randomized trials (analyzed separately) that evaluated postnatal steroids started from 28 days of life in preterm infants diagnosed with BPD. Certainty of evidence was assessed using the GRADE approach. Results: The search retrieved 9113 records, and 20 studies were included. Meta-analysis of the RCTs demonstrated that steroids significantly reduced oxygen requirement (daily mean difference of 1.6%, 95% CI 0.25–2.95), but the analysis did not identify significant differences in total duration of supplemental oxygen, length of stay, or mortality (moderate quality). From a safety perspective, steroids resulted in a transient increase in systemic blood pressure (mean difference of 6.8 mmHg, 95% CI 4.6–8.9) (moderate quality). Weight gain during treatment was lower in the systemic steroid group (−9.2 g/day, 95% CI −11.7 to −6.8) (moderate quality), although overall growth was reported as equal (2.4 g/day, 95% CI −0.3 to 6.3) (moderate quality). One retrospective study reported the incidence of steroid treatment among infants with established BPD (any definition) to be as high as 36%. Two single-arm studies reported a prolonged high-dose systemic steroid regimen as the routine treatment strategy for severe established BPD. Conclusions: Moderate quality of evidence suggests that steroid treatment cannot be recommended as standard of care for established BPD. However, corticosteroids are often used to this end. Large-scale RCTs designed to treat BPD are urgently needed. Furthermore, careful consideration for patient selection and compliance with GRADE methodology is essential. Full article

Cortisol measurement in dogs commonly supports the diagnosis of hypercortisolism or hypoadrenocorticism. Unlike serum cortisol, urine cortisol is less affected by daily fluctuations, and collection is non-invasive, making the urine cortisol-to-creatinine ratio (UCCR) a useful diagnostic tool. Immunoassays are commonly used but lack specificity for free, biologically active cortisol. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is recommended to overcome this limitation. This study aimed to validate an LC-MS/MS method for urinary cortisol measurement, establish a reference interval for UCCR in dogs, and compare the results with the commercial immunoassay system Immulite^® 2000 Xpi (Siemens, Cary, NC, USA). A comprehensive method validation was performed. Across different concentrations, the intra- and inter-assay coefficients of variation (CV) ranged from 2.39% to 9.45%, accuracy ranged from 87.7% to 105.5%, and bias varied from −12.3% to 5.53%, which were all within acceptable limits. The method demonstrated excellent linearity (r² ≥ 0.98), and stability under various conditions was satisfactory (RSD: −12.4% to 13.6%). Interference from endogenous and exogenous corticosteroids was negligible. The established reference interval for UCCR was 0.21–2.84 × 10⁻⁶. The exploratory comparison with the immunoassay revealed systematic and proportional differences between methods. The LC-MS/MS method demonstrated excellent analytical performance in terms of accuracy and specificity, and showed suitability for clinical application. Full article

Background/Objectives: Bullous pemphigoid (BP) is a manageable condition, and the primary goal of treatment is to control the disease while minimizing the use of corticosteroids due to their potential side effects with long-term use. The primary aim of this study was to assess the effectiveness of omalizumab (OMZ) treatment in bullous pemphigoid patients using both objective and subjective indicators, including bullous pemphigoid disease area index (BPDAI) score, peripheral eosinophil count, serum total IgE level, systemic corticosteroid dosage, and pruritus severity (VAS pruritus). The secondary aim was to explore potential predictors of treatment response, such as baseline BPDAI, age, gender, lesion distribution, serum total IgE, peripheral eosinophil count, maximum and minimum corticosteroid dose, and comorbidities, as well as to evaluate the time to clinical response and corticosteroid tapering. Methods: This retrospective analysis included 25 BP patients treated with OMZ as add-on therapy to systemic corticosteroids between January 2023 and December 2024 at Health Sciences University, Başakşehir Çam and Sakura Training and Research Hospital, Dermatology and Venerology Clinic. No other systemic immunosuppressants were permitted. All patients were already receiving systemic corticosteroids at enrolment. This retrospective analysis included 25 BP patients receiving omalizumab (300 mg/4 weeks) as an add-on to systemic corticosteroids, initiated primarily for steroid-refractory disease and/or persistent, sleep-disrupting pruritus. Baseline was defined immediately before the first OMZ dose; assessments were performed at baseline and week 12. Clinical (BPDAI, VAS pruritus) and laboratory (eosinophil count, total IgE levels) parameters were assessed at baseline and week 12. Results: OMZ treatment significantly reduced disease severity, as evidenced by a mean decrease in the BPDAI score of 105.0 ± 48.9 (95% CI 84.8–125.2) compared to baseline (p < 0.001). Peripheral eosinophil count also decreased by 0.6 ± 0.3 (95% CI 0.4–0.7) after treatment (p < 0.001). Total serum IgE levels declined significantly in 92% of patients (95% CI 244.5–2171.3) compared to pretreatment (p < 0.001), although two patients (8%) showed an increase (202.0 ± 258.8) after OMZ treatment. OMZ treatment led to a mean systemic corticosteroid dose reduction of 37.0 ± 14.1 mg (95% CI 31.1–42.8 mg), with a median corticosteroid tapering time of 4 weeks (3.0–4.0). Additionally, pruritus severity, measured by pruritus VAS, decreased by 6.2 ± 1.4 (95% CI 5.6–6.7) following treatment (p < 0.001). OMZ was well tolerated, with no serious adverse events. Conclusions: Within a 12-week observation window, we observed improvements in disease activity and pruritus alongside reduced corticosteroid exposure. Given the retrospective, uncontrolled add-on design, these findings do not establish causality but support further prospective controlled evaluation of omalizumab as a steroid-sparing option. Importantly, OMZ treatment significantly reduced the mean corticosteroid dose, pruritus VAS score, total IgE levels, and eosinophil count, indicating therapeutic activity and supporting its use as an effective steroid-sparing option in the management of bullous pemphigoid. Full article

Background/Objectives: Budesonide is a corticosteroid with low systemic bioavailability, commonly used for localized treatment in inflammatory bowel disease (IBD). While its short-term safety is well established, data on long-term effects—particularly regarding bone mineral density (BMD)—are limited. This study assessed the impact of prolonged oral budesonide use on BMD and related adverse events (AEs) in IBD patients. Methods: We retrospectively reviewed IBD patients treated with budesonide for ≥24 months who underwent baseline and follow-up DEXA scans. A matched control group with no history of budesonide use was selected. Clinical and biochemical data, along with DEXA scans, were collected. Changes in BMD of the femur and lumbar spine and BMD status (osteoporosis/osteopenia) were compared between the groups. Results: A total of 52 budesonide-treated patients (6 with ulcerative colitis and 46 with Crohn’s disease) and 52 matched controls were included. The mean disease duration of the budesonide group and the control group was 8.8 years and 9 years, respectively. Mean budesonide treatment duration was 46.1 ± 15.4 months (range: 25–94). No significant differences were observed between the control and treatment groups when the last BMD status was compared with the initial assessment. While femoral BMD remained stable in the budesonide group, it significantly declined in the control group (p = 0.019). L1-L4 BMD improved in the budesonide group (p = 0.002). The osteoporosis rate remained unchanged (OR: 0.136, 95% CI: 0.007–2.73, p = 0.19), while osteopenia decreased, favoring the budesonide group (OR: 0.197, 95% CI: 0.038–1.018, p = 0.05). No fragility fractures or systemic AEs occurred during follow-up. Conclusions: Long-term oral budesonide use in IBD appears safe with respect to BMD and is not associated with an increased risk of osteoporosis, osteopenia, or previously unrecognized AEs, even with treatment durations of up to four years. The slightly favorable outcome of BMD in IBD patients treated with budesonide needs further verification. Full article

Background/Objectives: Asthma remains a prevalent cause of emergency department (ED) visits worldwide, necessitating prompt and effective intervention to prevent severe morbidity and mortality. This study evaluates the management of asthma patients presenting to the ED, focusing on clinical assessment, treatment strategies, diagnostic evaluations, and discharge practices. Methods: This retrospective audit was conducted in a regional hospital in Queensland, Australia. All ED patients between July 2023 and June 2024 with a diagnosis of asthma were included. Findings were benchmarked against international asthma guidelines to assess adherence to best practice. Results: A total of 199 patients were included. This study found that bronchodilator therapy was administered in 92.5% of cases and systemic steroids were given to 73.4% of patients, aligning with guidelines. However, significant deficiencies were noted in using objective lung function assessments, with only 1% of patients undergoing peak expiratory flow measurement and none undergoing spirometry, despite guideline recommendations advocating for their routine use. Additionally, inhaled corticosteroid prescriptions upon discharge were recorded in 19.6% of cases, compared to the recommended target of over 80%. There was a 6% relapse rate within a month of ED discharge. Conclusions: These gaps indicate potential areas for improvement, particularly in structured airflow assessment and post-discharge asthma management. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs and the production of anti-double-stranded DNA (anti-dsDNA) antibodies. This study evaluated the associations between anti-dsDNA levels and smoking, oral corticosteroid (OCS) use, and immunosuppressive therapy in SLE patients. A retrospective monocentric analysis was performed on 119 SLE patients. Data on smoking history, OCS dosage, and immunosuppressive treatments were collected. Anti-dsDNA levels were assessed using fluorescent enzyme immunoassays and confirmed via indirect immunofluorescence. Smoking was significantly associated with higher anti-dsDNA levels (Spearman’s ρ = 0.292, p = 0.0014). Logistic regression identified pack-years (PPY) as a predictor of high anti-dsDNA levels (≥75 U/mL), with a 50% probability at 12.51 PPY and a 75% probability at 17.65 PPY (p < 0.001). OCSs were used by 58.82% of patients, with a median prednisone-equivalent dose of 5.0 mg; higher OCS doses correlated weakly but significantly with anti-dsDNA levels (R² = 0.066, p < 0.001). Anti-dsDNA levels differed across treatments (p = 0.027): MTX vs. AZA/MMF, and belimumab vs. AZA/MTX. Smoking, OCS use, and immunosuppressants influence anti-dsDNA levels. Belimumab showed greater reduction compared to conventional therapies. Personalized treatment strategies are needed, considering the effects of smoking and cortico-steroids. Full article

Dengue virus infection frequently involves the eye, manifesting with hemorrhages, uveal inflammation, retinal vascular changes and maculopathy. These ocular manifestations may arise during the acute febrile phase or emerge weeks later. Studies from endemic regions report that up to one-quarter of hospitalized patients develop eye-related symptoms. Furthermore, studies confirm a higher risk of new uveitis cases following dengue infection. Breakdown of the blood–ocular barrier—driven by antibody-mediated enhancement, complement activation and release of inflammatory mediators—leads to vascular leakage, tissue injury and ischemia. Diagnosis relies on clinical examination supplemented by imaging (OCT, angiography) and laboratory confirmation of dengue. Mild anterior inflammation often responds to topical steroids, while sight-threatening posterior disease requires systemic corticosteroids and, in refractory cases, immunomodulatory agents. Visual outcomes depend on the initial severity; anterior uveitis typically resolves without sequelae, whereas vasculitis or foveal involvement may leave lasting deficits. This review integrates the current understanding of dengue-related eye disease, emphasizing its varied presentations and the importance of early recognition. Further research into targeted, mechanism-based therapies is needed to optimize visual outcomes. Full article

Synovitis resolution is critical for joint homeostasis and prevents the progression of osteoarthritis (OA). Treatments like NSAIDs and intra-articular corticosteroids relieve symptoms by blocking pro-inflammatory mediators, but also impair the production of pro-resolving mediators, contributing to the likelihood of chronic synovitis. PPARγ signaling is an essential mechanism of synovitis resolution, which is decreased in OA tissues. To evaluate the potential of PPARγ agonists to promote pro-resolving pathways, equine macrophages cultured in autologous, normal, or inflamed synovial fluid (n = 10 horses) were treated with pioglitazone, geraniol, or both. Treatments modulated patterns of gene expression, increasing the expression of early drivers of resolution RELB and IL6, followed by increased NRF2 and PPARGC1A expression. Concentrations of TNF-α in conditioned synovial fluid significantly decreased as an early response to treatment, while IL10 concentrations also declined over time, suggesting increased tolerance to inflammatory stimuli and decreased compensatory feedback. Using an equine model of synovitis, intra-articular delivery of pioglitazone (n = 3 horses) or geraniol (n = 4 horses) was associated with decreased markers of synovium inflammation (geraniol) and enhanced cartilage proteoglycan preservation (geraniol and pioglitazone). In this small cohort of horses, no systemic or articular side effects were observed. Further studies optimizing treatment doses and regimens for intra-articular PPARγ agonism as a pro-resolving OA therapy are warranted. Full article