Search Results (854)

Background: Treatment compliant with the Global Initiative for Asthma (GINA) can promote more effective disease control. Single-inhaler triple therapy (SITT) is one method that is used to optimize therapy in this context, but TRIPLE therapy is still employed by physicians to a limited extent. Objective: This study aimed to describe the factors influencing challenges in optimizing asthma therapy. Methods: A 19-question survey, created via the CATI system, was distributed among pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland, Greece, Sweden, Slovenia, and Austria. Results: Statistically significant percentage differences in the use of TRIPLE therapy in the context of asthma management were observed among countries as well as between pulmonologists, allergists, and other specialists. Overuse of oral corticosteroids (OCSs) to treat nonsevere and severe asthma in the absence of an approach that focuses on optimizing inhalation therapy among asthma patients receiving TRIPLE therapy was observed in different countries as well as among physicians with different specialties. Twenty elements associated with the challenges involved in diagnosing and managing difficult-to-treat and severe asthma were identified. Six clinical categories for the optimization of asthma therapy via SITT were highlighted. The degree of therapeutic underestimation observed among severe asthma patients was assessed by comparing actual treatment with the recommendations of the GINA 2023 guidelines. Conclusions: Physicians of various specialties in Europe are subject to therapeutic inertia in terms of their compliance with the GINA 2023 guidelines. Full article

Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX), which functions to inhibit bacterial replication but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapy due to enhanced targeting and delivery. The extracellular matrix (ECM) has been shown to possess pro-regenerative and non-toxic properties in vitro, making it a promising delivery agent. The combination of LVX and ECM formed into nanoparticles may overcome barriers to lung delivery to effectively treat cystic fibrosis bacterial infections. Our goal is to advance CF care by providing a combined treatment option that has the potential to address both bacterial infections and lung damage. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The neutral charge and size of the particles may suggest their ability to attract toward and penetrate through the mucus barrier in order to target the bacteria. The NPs have also been shown to slow the drug dissolution, are non-toxic to human airway epithelial cells, and are effective in inhibiting Pseudomonas aeruginosa and Staphylococcus aureus. LVX-ECM NPs may be an effective treatment for pulmonary CF bacterial treatments. Full article

Lung cancer remains one of the most common and deadliest forms of cancer worldwide despite notable advancements in its management. Conventional treatments, such as chemotherapy, often have limitations in effectively targeting cancer cells, which frequently lead to off-target side effects. In this context, the pulmonary delivery of inhalable nanomaterials offers the advantages of being rapid, efficient, and target-specific, with minimal systemic side effects. This concise review summarizes the basic research and clinical translation of inhalable nanomaterials for the treatment of lung cancer. We also provide insights into the latest advances in pulmonary drug delivery systems, focusing on various types of pulmonary devices and nanomaterials. Furthermore, this paper discusses significant challenges in translating the discoveries of inhalable nanomaterials into clinical care for lung cancer and shares strategies to overcome these issues. Full article

Background: Probiotics are live microorganisms known for their health-promoting effects, particularly in modulating immune responses and reducing inflammation within the gastrointestinal tract. Emerging evidence suggests probiotics may also influence respiratory health, prompting investigation into their potential therapeutic application in lung inflammation. Methods: This study examined the anti-inflammatory effects of Ligilactobacillus salivarius (LS01 DSM 22775) and Bifidobacterium breve (B632 DSM 24706) on inflamed pulmonary epithelial cells. Lung carcinoma epithelial cells (A549) and normal bronchial epithelial cells (16HBE) were stimulated with IL-1β and treated with viable and heat-treated probiotics. Results: CCL-2 levels were significantly reduced by up to 40%, in A549 by viable form (10⁵–10⁷ AFU/g), instead of in 16HBE by heat-treated form (10⁷–10⁹ TFU/g). In A549 cells, TNF-α decreased by 20–80% with all formulations; instead, in 16HBE cells, IL-8 was reduced by viable strains (10⁷ AFU/g) by approximately 50%, while heat-treated strains (10⁹ TFU/g) decreased both IL-6 and IL-8 by 50%. All effective treatments completely inhibited IL-4 and eotaxin and suppressed NF-κB activation in both cell lines, with up to 80% reduction in phospho-p65 levels. In A549 cells, heat-treated strains fully blocked PGE2 production; instead, all four probiotics significantly inhibited COX-2 expression by approximately 50%. Conclusions: These findings demonstrate that both viable and heat-treated probiotics can modulate inflammatory responses in pulmonary epithelial cells, suggesting their potential application in inflammatory respiratory diseases. Heat-treated formulations may be particularly suited for local administration via inhalation, offering a promising strategy for targeting airway inflammation directly. Full article

Introduction: Radiomics is the extraction of non-invasive and reproducible quantitative imaging features, which may yield mineable information for clinical practice implementation. Quantification of lung function through radiomics could play a role in the management of patients with pulmonary lesions. The aim of this study is to test the capability of radiomic features to predict pulmonary function parameters, focusing on the diffusing capacity of lungs to carbon monoxide (DL_CO). Methods: Retrospective data were retrieved from electronical medical records of patients treated with Stereotactic Body Radiation Therapy (SBRT) at a single institution. Inclusion criteria were as follows: (1) SBRT treatment performed for primary early-stage non-small cell lung cancer (ES-NSCLC) or oligometastatic lung nodules, (2) availability of simulation four-dimensional computed tomography (4DCT) scan, (3) baseline spirometry data availability, (4) availability of baseline clinical data, and (5) written informed consent for the anonymized use of data. The gross tumor volume (GTV) was segmented on 4DCT reconstructed phases representing the moment of maximum inhalation and maximum exhalation (Phase 0 and Phase 50, respectively), and radiomic features were extracted from the lung parenchyma subtracting the lesion/s. An iterative algorithm was clustered based on correlation, while keeping only those most associated with baseline and post-treatment DL_CO. Three models were built to predict DL_CO abnormality: the clinical model—containing clinical information; the radiomic model—containing the radiomic score; the clinical-radiomic model—containing clinical information and the radiomic score. For the models just described, the following were constructed: Model 1 based on the features in Phase 0; Model 2 based on the features in Phase 50; Model 3 based on the difference between the two phases. The AUC was used to compare their performances. Results: A total of 98 patients met the inclusion criteria. The Charlson Comorbidity Index (CCI) scored as the clinical variable most associated with baseline DL_CO (p = 0.014), while the most associated features were mainly texture features and similar among the two phases. Clinical-radiomic models were the best at predicting both baseline and post-treatment abnormal DL_CO. In particular, the performances for the three clinical-radiomic models at predicting baseline abnormal DL_CO were AUC₁ = 0.72, AUC₂ = 0.72, and AUC₃ = 0.75, for Model 1, Model 2, and Model 3, respectively. Regarding the prediction of post-treatment abnormal DL_CO, the performances of the three clinical-radiomic models were AUC₁ = 0.91, AUC₂ = 0.91, and AUC₃ = 0.95, for Model 1, Model 2, and Model 3, respectively. Conclusions: This study demonstrates that radiomic features extracted from healthy lung parenchyma on a 4DCT scan are associated with baseline pulmonary function parameters, showing that radiomics can add a layer of information in surrogate models for lung function assessment. Preliminary results suggest the potential applicability of these models for predicting post-SBRT lung function, warranting validation in larger, prospective cohorts. Full article

Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events. Full article

Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus aureus (S. aureus) infections in patients with BE, but this is unexplored. We examined the association between ICS use prior to BE diagnosis at different doses and the risk of S. aureus isolation in patients with BE. Methods: We conducted a national register-based cohort study including Danish patients with a BE diagnosis code between 2001 and 2018 with a 1-year follow-up time from the date of diagnosis. ICS exposure was categorized based on accumulated prescriptions redeemed 365 days before BE diagnosis and divided into none, low, moderate, or high use based on clinically relevant doses. A cause-specific Cox proportional hazards regression model was used to estimate the risk of S. aureus isolation. A sensitivity analysis, an inverse probability of treatment weighted model (IPTW), was performed. Results: A total of 5093 patients were included in this study. S. aureus was isolated in 156 patients (3.1%). High-dose ICS was associated with an increased risk of S. aureus isolation, HR 3.81 (95% CI 2.51; 5.79). No association for low or moderate use was found, low-dose HR 1.22 (95% CI 0.77; 1.93), and moderate-dose HR 1.24 (95% CI 0.72; 2.16). IPTW analysis yielded similar results. Conclusions: High-dose ICS use in patients with BE was associated with an increased risk of S. aureus isolation. ICS should be used cautiously in patients with BE. Full article

About a quarter of the world’s population is infected with Mycobacterium tuberculosis. Growing antibiotic resistance by this microorganism is a major problem in the therapy of the disease. M. avium-M. intracellulare that emerged as a major opportunistic infection of HIV/AIDS continues to afflict immunocompromised individuals. We describe the use of liposome-encapsulated antibiotics in the experimental and clinical therapy of mycobacterial infections, as well as recent experimental liposomal vaccines against tuberculosis. Liposome-mediated intravenous or inhalational delivery of antibiotics enhances the antibacterial effects of the drugs, particularly for infections of resident macrophages, where the liposomes are passively targeted. Despite experimental successes of liposomal antibiotics in the treatment of mycobacterial and other bacterial infections, applications of this method to the clinic have been lagging. This review underscores the significance of liposomes in the treatment of mycobacterial infections, encompassing their synthesis methods, limitations, and both preclinical and clinical studies, providing guidance for the development of future therapeutic approaches and innovative antimicrobial strategies. Full article

Background: Inhaled corticosteroids (ICSs) are a cornerstone in asthma management, particularly during exacerbations, when high doses are often prescribed. However, patient concerns about potential side effects such as increased appetite, weight gain, and metabolic disturbances may reduce adherence, compromising treatment outcomes. While oral corticosteroids (OCSs) are well known to induce such effects, the metabolic impact of short-term high-dose ICSs remains poorly studied. Objective: This prospective pilot study aimed to assess whether a 14-day course of high-dose ICSs in adults with stable asthma induces changes in appetite, dietary intake, leptin levels, or body weight. Methods: Thirty-five adults (19 males, 16 females; mean age 48.7 ± 15.1 years) with stable mild asthma received ≥400 µg/day extrafine beclomethasone dipropionate/formoterol via pressurized metered-dose inhaler for 14 days. Participants underwent assessments at baseline and after 14 days, including body weight, BMI, fasting serum leptin levels, dietary intake (evaluated using 24 h dietary recalls), and appetite (measured via a visual analogue scale). Results: No significant changes were observed in body weight (mean change: −0.38 kg; 95% CI: −0.81 to 0.05; p = 0.083) or BMI (p = 0.912) following high-dose ICS use. Similarly, serum leptin levels (mean change: 0.13 ng/mL; 95% CI: −3.47 to 3.72; p = 0.945), subjective appetite scores (mean change: −4.93 mm; 95% CI: −13.64 to 3.79; p = 0.267), and dietary energy intake (mean change: +255 kJ/day; 95% CI: −380 to 891; p = 0.431) did not differ significantly post-intervention. Conclusions: Short-term high-dose ICS therapy in adults with mild asthma may not significantly affect appetite, dietary intake, leptin levels, or body weight. These findings support the metabolic safety of short-term high-dose ICSs and may help alleviate patient concerns, improving adherence during exacerbation management. Full article

Background: Allergic rhinitis (AR) is a prevalent allergic disorder characterized by a complex pathogenesis. Drawing on traditional Chinese medicine theory and contemporary pharmacological principles, this study developed an inhalation-based herbal formulation, ZHW, to explore a novel non-invasive therapeutic approach. Objective: To investigate the therapeutic effects of ZHW on AR and elucidate its underlying mechanisms and potential targets through an integrated analysis of network pharmacology and proteomics. Materials and Methods: The volatile components of ZHW were analyzed by gas chromatography–mass spectrometry (GC-MS). The mouse model of AR was induced by OVA sensitization. The therapeutic efficacy of ZHW was assessed based on nasal symptom scores, histopathological examination, and inflammatory cytokine levels. Furthermore, the underlying mechanisms and potential targets of ZHW were investigated through integrated network pharmacology and proteomics analyses. Results: GC-MS analysis identified 39 bioactive compounds in ZHW. Inhalation treatment with ZHW demonstrated significant anti-allergic effects in OVA-sensitized mice, as evidenced by (1) reduced sneezing frequency and nasal rubbing behaviors; (2) decreased serum levels of IL-4, histamine, and OVA-specific IgE; (3) attenuated IL-4 concentrations in both nasal lavage fluid and lung tissue; (4) diminished nasal mucosal thickening; and (5) suppression of inflammatory cell infiltration. Integrated network pharmacology and proteomics analyses indicated that ZHW’s therapeutic effects were mediated through the modulation of multiple pathways, including the PI3K-Akt signaling pathway, the B cell receptor signaling pathway, oxidative phosphorylation, and the FcεRI signaling pathway. Key molecular targets involved Rac1, MAPK1, and SYK. Molecular docking simulations revealed strong binding affinities between ZHW’s primary bioactive constituents (linalool, levomenthol, linoleic acid, Linoelaidic acid, and n-Valeric acid cis-3-hexenyl ester) and these target proteins. Conclusions: The herbal formulation ZHW demonstrates significant efficacy in alleviating allergic rhinitis symptoms through multi-target modulation of key signaling pathways, including PI3K-Akt- and FcεRI-mediated inflammatory responses. These findings substantiate ZHW’s therapeutic potential as a novel, non-invasive treatment for AR and provide a strong basis for the development of new AR therapies. Future clinical development will require systematic safety evaluation to ensure optimal therapeutic outcomes. Full article

Background: Nausea and vomiting frequently occur during postoperative recovery, chemotherapy, and pregnancy. While peppermint oil is traditionally used to relieve these symptoms, its efficacy remains uncertain. This systematic review and meta-analysis evaluates the efficacy of peppermint oil inhalation for postoperative (PONV), chemotherapy-induced (CINV), and pregnancy-related nausea and vomiting (NVP). Methods: Following PRISMA guidelines, we searched five databases (Scopus, Embase, the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science) in November 2022, with an update in December 2024. Randomised controlled trials were included, comparing peppermint oil inhalation to a control in patients with PONV, CINV, and NVP. Separate meta-analyses were conducted for each patient group using R, focusing on the severity of the nausea and vomiting. Results: Nineteen RCTs were included. In three PONV studies, peppermint oil inhalation was associated with a reduction in nausea 2 to 6 h after the intervention (MD: −0.60 points, 95% confidence interval (CI): −0.77 to −0.44, p = 0.004). In three NVP studies, daily peppermint oil treatment was linked to lower symptom severity at 48 h (MD: −0.51, 95% CI: −0.78 to −0.24, p = 0.015) and 96 h (MD: −0.68, 95% CI: −1.09 to −0.27, p = 0.019). In three CINV studies, peppermint oil inhalation appeared to reduce symptoms at all time points, with the most notable reduction at 48 h (MD: −2.23, 95% CI: −3.13 to −1.34, p < 0.001) and 72 h (MD: −2.41, 95% CI: −3.96 to −0.86, p = 0.010). Conclusions: Peppermint oil inhalation may be a promising complementary therapy for reducing nausea and vomiting in postoperative, chemotherapy, and pregnancy settings. Full article

Background/Objectives: The integration of machine learning (ML) and artificial intelligence (AI) has revolutionized the pharmaceutical industry by improving drug discovery, development and manufacturing processes. Based on literature data, an ML model was developed by our group to predict the formation of binary co-amorphous systems (COAMSs) for inhalation therapy. The model’s ability to develop a dry powder formulation with the necessary properties for a predicted co-amorphous combination was evaluated. Methods: An extended experimental validation of the ML model by co-milling and X-ray diffraction analysis for 18 API-API (active pharmaceutical ingredient) combinations is presented. Additionally, one COAMS of rifampicin (RIF) and ethambutol (ETH), two first-line tuberculosis (TB) drugs are developed further for inhalation therapy. Results: The ML model has shown an accuracy of 79% in predicting suitable combinations for 35 APIs used in inhalation therapy; experimental accuracy was demonstrated to be 72%. The study confirmed the successful development of stable COAMSs of RIF-ETH either via spray-drying or co-milling. In particular, the milled COAMSs showed better aerosolization properties (higher ED and FPF with lower standard deviation). Further, RIF-ETH COAMSs show much more reproducible results in terms of drug quantity dissolved over time. Conclusions: ML has been shown to be a suitable tool to predict COAMSs that can be developed for TB treatment by inhalation to save time and cost during the experimental screening phase. Full article

Background and Objectives: The worldwide shift toward psychiatric deinstitutionalization has aimed to enhance patient autonomy, social integration, and overall quality of life. However, limited studies have examined how concurrent substance use—particularly alcohol, marijuana, and inhalable drugs—affects clinical outcomes in these populations. This study aimed to evaluate psychiatric patients with varying degrees of institutionalization and investigate whether substance use complicates or exacerbates treatment outcomes. We hypothesized that individuals using substances would demonstrate worse psychosocial functioning, higher healthcare costs, and increased readmission rates. Methods: We performed a cross-sectional study of 95 participants recruited from long-term care facilities. Participants completed the SF-36 survey validated in Romanian. Financial data were collected to gauge direct and indirect healthcare expenditures. Results: Results indicated that 34.7% of participants reported alcohol use, 12.6% used marijuana, and 9.5% used inhalable substances. Substance-using patients experienced higher mean hospitalization costs of approximately USD 3251.8, compared to non-users (USD 2743.6, p = 0.032). Quality-of-life scores were significantly lower among substance users (mean SF-36 score 58.4 vs. 66.7, p = 0.027). Rates of relapse and readmission were also notably higher in the substance-using cohort (42.1%) relative to non-users (29.8%, p = 0.041). Conclusions: To our knowledge, this is the first Romanian study—and one of only a handful in Europe—to quantify how specific substance-use profiles simultaneously alter quality of life and direct healthcare costs in a deinstitutionalized psychiatric population. Our findings highlight the need for integrated interventions targeting both mental health and substance abuse. Full article

The use of dry powder inhalers (DPIs) represents a cornerstone in the treatment of chronic pulmonary diseases. However, suboptimal inhalation techniques, including inadequate airflow rates, have been a persistent concern for achieving effective therapeutic outcomes, as many patients remain unaware of their insufficient inhalation performance. As an effective strategy, a digital monitoring system, coupled with dry powder inhalers (DPIs), has emerged to estimate flow profiles and provide inhalation information. The estimation could be further facilitated by the application of artificial intelligence (AI). In this work, a novel digital system to primarily monitor pressure during DPI usage was successfully designed, and advanced machine learning (ML) techniques were then employed to estimate inhalation flow profiles based on the captured data. Four optimal machine learning models were selected for subsequent inhalation parameter prediction, given their superior generalization ability. By using these models, inhalation flow profiles could be successfully estimated, with an excellent accuracy of 97.7% for Peak Inspiratory Flow Rate (PIFR) and 95.2% for inspiratory capacity (IC). In summary, the pressure-based digital monitoring system empowered by AI techniques could be successfully applied to assess inhalation flow profiles with excellent accuracy. Full article

Background and Objectives: The common complaints of head and neck cancer patients receiving concurrent chemo-radiotherapy (CCRT) are dry mouth, dysphagia, trismus, hoarseness, sore throat, and oral mucosal damage, which result in retained secretions and difficult expectoration. We aimed to investigate the effect of adjuvant respiratory therapy on secretion expectoration and treatment completion in patients with head and neck cancer receiving CCRT. Materials and Methods: From November 2016 to May 2018, 56 head and neck cancer patients were recruited retrospectively, and according to their respiratory therapy in the medical record, were divided into the control group (CG, n = 27) or the research group (RG, n = 29). In the CG, the patients were treated via the teaching of routine breathing exercises and expel techniques, while patients in the RG were treated with the inhalation of a ß-agonist bronchodilator agent five times each week, in addition to the standard treatment administered in the CG. Results: The total completion rate of treatment was significantly higher in the RG (21 patients) compared with the CG (12 patients) (72.4% vs. 44.4%, p < 0.05). After therapy, the rates of clinical symptoms were significantly increased in the RG compared with the CG, including smooth expectoration (76.2% vs. 75.0%), decreased secretions (61.9% vs. 58.3%), reduced viscosity of secretions (66.7% vs. 58.3%), lower cough frequency (71.4% vs. 50.0%), improved sore throat (52.4% vs. 41.7%), and swallowing function (52.4% vs. 50.0%). The continuation of chemo-radiotherapy without disruption was higher in the RG than it was in the CG (66.7% vs. 50.0%). There was no significant difference in adverse effects between the two groups. Conclusions: Adjuvant respiratory therapy not only improves secretion expectoration, but also reduces side effects, thus promoting the completion of the CCRT schedule in patients with head and neck cancer. Full article