Asthma Clinical Outcomes Research Articles

Formulation and evaluation of carrier-based dry powders containing budesonide and arformoterol for inhalation therapy

ABSTRACT Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health issues, with inhalation therapy being a primary treatment method. However, dry powder inhalers (DPIs) often face the issue of drug particle aggregation, which can reduce drug delivery efficiency. This study aims to investigate particle aggregation and optimize the cohesion–adhesion balance to improve inhalation efficiency. Advanced techniques such as atomic force microscopy and Raman imaging were employed to analyze particle interactions and aggregation behavior, focusing on lactose ratios, particle shapes, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing Budesonide (BUD) and Arformoterol (AFT) was evaluated in an asthma model. Specifically, sRAW, neutrophil count, and tidal volume values were significantly improved compared to the positive control group, with p-values below 0.01. AFT demonstrated equivalent efficacy to Formoterol at half the dose. Additionally, pharmacokinetic (PK) studies showed that both drugs exhibited similar in vivo behavior, confirming the therapeutic superiority of AFT. (p-value for AUC0-t and Cmax: 0.646 and 0.153, respectively) The key findings highlight that formulation optimization significantly reduces particle aggregation and improves drug delivery efficiency in DPI (FPF for AFT and BUD: 39.4% and 50.6%, respectively), suggesting the potential for enhanced clinical outcomes in asthma and COPD patients. This study provides valuable insights for the formulation development of inhalable therapies.

Late-Onset Asthma: A Review

Asthma is a chronic respiratory condition with a growing global prevalence, affecting millions of individuals annually. While asthma can develop at any age, late-onset asthma is a specific phenotype that begins in adulthood, as recognized by the Global Initiative for Asthma (GINA) in its 2024 guidelines. This form of asthma is often associated with several predisposing factors, including gender, obesity, occupational exposure, rhinitis, respiratory infections, smoking, stress, and diminished lung function. Unlike early-onset asthma, which frequently involves a history of allergies, late-onset asthma tends to lack allergic triggers, making it a distinct and challenging form of the disease. Managing late-onset asthma is often more complex, as it typically requires higher doses of corticosteroids and demonstrates a reduced responsiveness to standard steroid treatments. The exact mechanisms and pathophysiological processes contributing to the increased severity and poorer clinical outcomes in late-onset asthma remain largely unclear. This uncertainty often leads to underdiagnosis and inadequate management, further complicating patient care. Phenotypic analysis is recommended to improve treatment outcomes. This includes assessing clinical features and utilizing biomarkers, such as inflammatory markers and immunoglobulin E (IgE) levels, to guide targeted therapy when conventional steroid treatments are insufficient. However, there is a significant need for further research to elucidate the underlying mechanisms of late-onset asthma. This literature review is essential to develop more effective, personalized treatment strategies that can address the unique challenges posed by this asthma phenotype, ultimately leading to better management and improved patient outcomes.

Clinical remission and control in severe asthma: agreements and disagreements.

Over the last two decades, we have witnessed great advancements in our understanding of the immunological pathways of asthma, leading to the development of targeted therapies, such as biologic drugs, that have radically and definitively changed the clinical outcomes of severe asthma. Despite the numerous therapeutic options available, ~4-10% of all people with asthma have severe or uncontrolled asthma, associated with an increased risk of developing chronic oral corticosteroid use, fixed airflow limitation, exacerbations, hospitalization and, finally, increased healthcare costs. The new concept of disease modification in asthma comes from the evolution of asthma management, which encompasses phenotyping patients with different inflammatory endotypes characterizing the disease, followed by the advent of more effective therapies capable of targeting the proximal factors of airway inflammation. This treat-to-target approach aims to achieve remission of the disease. Because the novel treatment paradigm for severe asthma with the advent of biologic therapies is no longer clinical control but rather clinical remission - a step closer to the concept of cure - a deeper and more accurate understanding of the critical causal mechanisms and endotypes of asthma is necessary to achieve the goal of clinical remission, which has the potential to generate real life-changing benefits for patients. This review aims to frame the evolution of the debated concept of clinical remission and provide clinicians with insights that may be helpful in achieving remission in the greatest number of patients.

Demographic and Asthma-Related Characteristics of Asthmatics Using Pressurized Metered Dose Inhalers and Dry Powder Inhalers.

Background: Asthma controller medications can be delivered via pressurized metered dose inhaler (pMDI) or dry powder inhaler (DPI) devices. Objective: This study aimed to evaluate the frequency of exacerbations and satisfaction rate with device use in asthmatics using pMDIs or DPIs. Methods: A multicenter, cross-sectional study was conducted in adults who used pMDIs or DPIs with correct inhaler technique and good adherence for asthma treatment. Demographic and asthma-related characteristics of the subjects and data regarding device satisfaction were collected through a face-to-face interview in the outpatient clinic. Rates of pMDI and DPI users and the data were compared between the two groups. Results: The study included 338 patients (mean age: 48.6 ± 14.5 years, 253 [74.9%] women). Among participants, 96 (28.4%) were using pMDI and 242 (71.6%) were using DPI. The age of patients using pMDI were significantly lower compared with DPI users. No significant difference was observed in terms of device satisfaction and clinical outcomes of asthma between pMDI and DPI users with good inhaler technique and good adherence. Conclusion: More asthmatics use DPIs, however, pMDIs are used in younger asthmatic patients. No significant difference in terms of device satisfaction and clinical outcomes of asthma was observed between pMDI and DPI users.

Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study.

Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients. This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use. Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines. In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients. These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma.

Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation.

Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.

Effects of Moderate- Versus Vigorous-Intensity Exercise Training on Asthma Outcomes in Adults

The therapeutic effects of exercise have prompted calls for it to be embedded into standard asthma care, but evidence informing the optimal exercise intensity is lacking. This study aimed to compare the effects of moderate- and vigorous-intensity aerobic exercise training on asthma outcomes and inflammation. This was a 12-week randomized controlled trial in 46 adults with asthma randomized to either (1) 45-minute moderate-intensity exercise training 3 times/wk, (2) 30-minute vigorous-intensity exercise training 3 times/wk, or (3) the control group. Asthma-related quality of life (AQLQ), asthma control (ACQ), cardiorespiratory fitness, body composition, and airway and systemic inflammation were assessed before and after the intervention. Forty-one participants completed the study (89% retention). The moderate-intensity group had a statistically and clinically significant improvement in AQLQ (0.63 [0.33-0.93], P < .001) and ACQ (-0.51 [-0.83 to -0.19], P= .003) relative to control. The vigorous-intensity group had a statistically, but not clinically, significant improvement in AQLQ (0.46 [0.14-0.80], P= .007) and ACQ (-0.36 [-0.69 to -0.02], P= .040) relative to control. After moderate-intensity training, there was a reduction in sputum macrophage (-1341 [-2491 to -191]× 104/mL, P= .024) and lymphocyte (-114 [-220 to -8]× 104/mL, P= .036) counts relative to control. A reduction in android fat mass, but not a change in fitness, was associated with improved AQLQ (rs= -0.341, P= .030) and reduced sputum IL-6 (rs= 0.422, P= .013). Our findings suggest that both moderate-intensity and vigorous-intensity aerobic exercise training are associated with improvements in clinical asthma outcomes and, therefore, both intensities could be recommended as an adjuvant asthma therapy.

Asthma patients' and physicians’ perspectives on the burden and management of asthma: Post-hoc analysis of APPaRENT 1 and 2 to assess predictors of treatment adherence

IntroductionPatient adherence to maintenance medication is critical for improving clinical outcomes in asthma and is a recommended guiding factor for treatment strategy. Previously, the APPaRENT studies assessed patient and physician perspectives on asthma care; here, a post-hoc analysis aimed to identify patient factors associated with good adherence and treatment prescription patterns. MethodsAPPaRENT 1 and 2 were cross-sectional online surveys of 2866 adults with asthma and 1883 physicians across Argentina, Australia, Brazil, Canada, China, France, Italy, Mexico, and the Philippines in 2020–2021. Combined data assessed adherence to maintenance medication, treatment goals, use of asthma action plans, and physician treatment patterns and preferences. Multivariable logistic regression models assessed associations between patient characteristics and both treatment prescription (by physicians) and patient treatment adherence. ResultsPatient and physician assessments of treatment goals and adherence differed, as did reporting of short-acting β2-agonist (SABA) prescriptions alongside maintenance and reliever therapy (MART). Older age and greater patient-reported severity and reliever use were associated with better adherence. Patient-reported prescription of SABA with MART was associated with household smoking, severe or poorly controlled asthma, and living in China or the Philippines. ConclusionsResults revealed an important disconnect between patient and physician treatment goals and treatment adherence, suggesting that strategies for improving patient adherence to maintenance medication are needed, focusing on younger patients with milder disease. High reliever use despite good adherence may indicate poor disease control. Personalised care considering patient characteristics alongside physician training in motivational communication and shared decision-making could improve patient management and outcomes.

Bronchial Cryo-Denervation for Severe Asthma: A Pilot Study

Introduction: Targeting the parasympathetic nervous system innervating the airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation in the lung. Methods: A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study. Patients underwent bifurcated BCD treatment at a 30-day interval after baseline assessment. Follow-up through 12 months included assessment of adverse events, technical feasibility, and changes in pulmonary function; asthma control questionnaire-7 (ACQ-7); and asthma control test (ACT). Results: BCD was performed on all 15 severe asthma patients, with technical feasibility of 96.7%. There were no device-related and 2 procedure-related serious adverse events through 12 months, which resolved without sequelae. The most frequent nonserious procedure-related adverse event was increased cough in 60% (9 of 15) patients. Pulmonary function remained unchanged, and significant improvements from baseline ACQ-7 (mean, −1.19, p = 0.0032) and ACT (mean, 3.18, p = 0.0011) scores were observed since the first month’s follow-up after a single lung airway treatment, with similar trends till the end of the 12-month follow-up. Conclusion: This study provides the first clinical evidence of the safety, feasibility, and initial efficacy of BCD in patients with severe asthma.

Small airway dysfunction measured by impulse oscillometry is associated with exacerbations and poor symptom control in patients with asthma treated in a tertiary hospital subspecialist airways disease clinic.

Small airways dysfunction contributes to asthma pathophysiology and clinical outcomes including exacerbations and asthma control. Respiratory oscillometry is a simple, non-invasive and effort independent lung function test that provides vital information about small airway function. However, interpretation and clinical utility of respiratory oscillometry has been in part limited by lack of agreed parameters and the respective cutoffs. The aim of this study was to determine the prevalence of small airways dysfunction based on published impulse oscillometry (IOS) definition in patients with asthma referred to a tertiary asthma clinic and the extent to which it correlates with asthma clinical outcomes. We retrospectively reviewed the medical records of all patients with asthma managed in the severe asthma clinic between January 2019 and December 2022 who underwent routine lung function tests with oscillometry and spirometry. Small airways dysfunction was determined from various published IOS parameter cutoffs, and the data were analysed to determine correlations between IOS parameters and asthma outcomes. Amongst the 148 patients, the prevalence of small airways dysfunction ranged from 53% to 78% depending on the defining oscillometry parameter. All oscillometry parameters correlated with the severity of airflow obstruction (FEV1% predicted, p < 0.001). Several oscillometry parameters correlated with asthma symptom burden, the strongest correlation was seen for frequency dependent resistance (R5-R20) with scores of Asthma Control Questionnaire (ACQ6) (Spearman's rank coefficient 0.213, p = 0.028) and Asthma Control Test (ACT) (Spearman's rank coefficient -0.248, p = 0.012). R5-R20 was predictive of poor asthma control defined by ACQ6 >1.5 (OR 2.97, p = 0.022) or ACT <20 (OR 2.44, p = 0.055). Small airways dysfunction defined by R5-R20 and area under the reactance curve (AX) also significantly increases asthma exacerbation risk (OR 2.60, p = 0.02 and OR 2.31, p = 0.03 respectively). Respiratory oscillometry is a sensitive measure of small airways dysfunction that should complement spirometry in the routine assessment of asthma. Small airways dysfunction is highly prevalent in patients with asthma referred to a tertiary asthma clinic. R5-R20 was the metric most predictive in identifying patients at risk of asthma exacerbations and poor asthma control.

Real-World Effectiveness of Statin Therapy in Adult Asthma

Blood lipids affect airway inflammation in asthma. Although several studies have suggested anti-inflammatory effects of statins on asthmatic airways, further studies are needed to clarify the long-term effectiveness of statins on asthma control and whether they are an effective treatment option. To evaluate the long-term effectiveness of statins in the chronic management of adult asthma in real-world practice. Electronic medical record data spanning 28 years, collected from the Ajou University Medical Center in Korea, were used to conduct a retrospective study. Clinical outcomes were compared between patients with asthma who had maintained statin use (the statin group) and those not taking statins, whose blood lipid tests were always normal (the non-statin group). We performed propensity score matching and calculated hazard ratios with 95% CIs using the Cox proportional hazards model. Severe asthma exacerbation was the primary outcome; asthma exacerbation, asthma-related hospitalization, and new-onset type 2 diabetes mellitus and hypertension were secondary outcomes. After 1:1 propensity score matching, the statin and non-statin groups each included 545 adult patients with asthma. The risk of severe asthma exacerbations and asthma exacerbations was significantly lower in the statin group than in the non-statin group (hazard ratios [95% CI]= 0.57 [0.35-0.90] and 0.71 [0.52-0.96], respectively). There were no significant differences in the risk of asthma-related hospitalization or new-onset type 2 diabetes mellitus or hypertension between groups (0.76 [0.53-1.09], 2.33 [0.94-6.59], and 1.71 [0.95-3.17], respectively). Statin use is associated with a lower risk of asthma exacerbation, with better clinical outcomes in adult asthma.

Pharmacists in Australian general practice: Discussion of the findings of an evaluation from 2016 to 2021

AbstractPharmacists embedded in general practice can improve medicines optimisation and patient safety, but Australia has been slower to adopt and fund this model than other comparable countries. Over the last decade there have been various local programs integrating pharmacists in general practice across Australia. This article summarises the results of an evaluation in Canberra from 2016–2021. Pharmacists predominantly conducted clinical activities, including medication reviews and clinical audits. General practitioner (GP) acceptance and implementation of medication review recommendations was high (75%). General practice pharmacists were able to achieve positive clinical outcomes in asthma and smoking cessation. Surveys and interviews identified that the general practice pharmacist role was welcomed by patients, GPs, and other healthcare professionals. Patient satisfaction was very high, with patients supporting the expansion of this pharmacy service. Collaboration between the pharmacists and other healthcare professionals was high. Some pharmacists left employment in general practice after less than a year. Introducing a clear job description could be beneficial in retaining pharmacists, improving trust and working relationships, and enhancing collaboration. The majority of clinical activities conducted by the pharmacists had the potential to improve patient care and decrease healthcare costs. Apart from healthcare savings, benefit–cost ratios of income generated and costs reduced by pharmacists when compared to salaries suggested that pharmacists may be cost‐beneficial in some scenarios. Absence of funding for this model of care remains a barrier to wider adoption in Australia and needs addressing. This study was approved by the University of Canberra Human Research Ethics Committee (Project number: 15–235) and funded under the Primary Health Network Program (Grant number: 25097479).

Dietary Inflammatory Index and Clinical Outcome Measures in Adults With Moderate-to-Severe Asthma

Diet is increasingly recognized as a modifiable factor in lung health, predominantly due to the immunomodulatory effects of nutrients. The Dietary Inflammatory Index (DII) is a score developed to express the inflammatory potential of a diet. We aimed to assess the association of the DII and food groups, with clinical, functional, and inflammatory asthma outcomes in adults with asthma. Patients with moderate-to-severe asthma were included in this cross-sectional study between June 2019 and October 2021, and completed a 3-day food diary, to calculate the DII and intake of food groups (ie, fruits, whole grains, processed meats, and sugar-sweetened beverages). Functional outcomes included pulmonary function tests and the 6-minute walking distance, whereas clinical outcomes were assessed usingquestionnaires on asthma control, quality of life, and health care utilization. Inflammatory markers were exhaled nitric oxide and blood leukocytes, eosinophils, and IL-6. Multivariable regression analyses were used to examine theassociation of DII and food groups with asthma outcomes. A total of 109 patients participated (35% male, mean ± standard deviation age 51.8 ± 14.2 years, body mass index 27.4 ± 5.3 kg/m2). Overall, 62% had a DII score >0, indicating a proinflammatory diet, which was not related to asthma severity. A more proinflammatory diet was consistently associated with lower forced vital capacity (%pred), but inconsistent results were observed with respect to airway obstruction. Neither the DII nor food groups were associated with clinical outcomes. Except for higher levels of exhaled nitric oxide in relation to an anti-inflammatory diet, we found no associations between inflammatory markers and the DII. Results from this cross-sectional study among patients with moderate-to-severe asthma do not support the hypothesis that a proinflammatory diet is associated with worse asthma outcomes, although limitations in study design and dietary intake estimation should be considered. Future well-designed experimental studies are needed to assess whether targeting the inflammatory potential of diet could lead to better outcomes in adults with asthma.

Frailty Prevalence and Association with Clinical Outcomes in Interstitial Lung Disease, Asthma, and Pleural Disease.

Frailty is a syndrome characterised by increased vulnerability to negative outcomes. Interstitial lung disease (ILD), asthma, and pleural disease are leading causes of morbidity and mortality. We aimed to investigate the prevalence and impact of frailty in adult patients with these diseases. We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, The Cochrane Library, and EMBASE for studies reporting on frailty in ILD, asthma, and pleural disease. MeSH terms including interstitial lung disease, Idiopathic Pulmonary Fibrosis, Non-specific Interstitial Pneumonia, Chronic Hypersensitivity Pneumonitis, systemic sclerosis-associated ILD, connective tissue disease-associated ILD, and frailty were used as key words. The primary outcome was prevalence of frailty. Where enough contextually homogeneous studies were included, a pooled random-effects meta-analysis was performed with mortality and hospitalisation as the outcomes. The review found three studies relating to frailty in asthma. No studies relating to pleural disease and frailty were identified. The median prevalence in asthma was 9.5% (IQR, 7.8-11.3). Six relevant studies incorporating 1471 ILD patients (age 68.3 ± SD2.38; 50% male) were identified, which were either cohort or cross-sectional design rated either good or fair. The median prevalence of frailty was 48% (IQR, 25-50). There was a positive association between frail ILD patients and increased risk of long-term mortality (pooled OR, 2.33 95%CI 1.31-4.15, I2 9%). One study reported a hospitalization rate of HR = 1.97(1.32-3.06) within 6 months in frail ILD patients. Frailty is very common and associated with increased mortality in patients with ILD. There are still minimal data regarding the prevalence of frailty and its influence on the risk in this population.

Effectiveness of long term therapy of inhaled Steroids in Childhood Asthma: A Systemic Review

Asthma exacerbations are a common and important cause of attendance at emergency departments and subsequent hospital admissions. This systemic review aimed to evaluate the effectiveness of long term therapy of inhaled steroids in childhood asthma. A search of PubMed (Medline) from January 1996 through February 2021 by using the keywords inhaled steroids in childhood asthma, identified potential studies. All randomized controlled trials and clinical trials of prophylactic inhaled steroid therapy for childhood asthma that included data on clinical outcomes (symptoms improvement and concomitant drug use) or laboratory outcomes (peak expiratory flow rate PEFR and (or) forced expiratory volume in first second FEV1) were included. Studies of children (?18?years old) with mild-to-moderate chronic or persistent asthma will be included.Results: In total, 15 of 116 studies met the inclusion criteria. Inhaled corticosteroids (ICS)versus placebo(3studies): ICS show good control on bronchial asthma by ratio(66.7%) and there was no improvement by placebo.ICS versus Mast cell stabilizer (DSCG, cromolyn sodium or nedocromil)(6 studies): by ICS there was better control of asthma, lower of airway hyperresponsivness, decrease risk for hospitalization in comparing to mast cell stabilizers by ratio of (66.7%).ICS versus LTRA (Montelukast)(3 studies) : by ICS better control of symptoms, modified exacerbation risk, improvement of pulmonary function in comparing to LTRA by ratio of (66.7%).ICS versus OCS (2 studies):more rapid clinical improvement results by OCS (50%), more improvement in the inflammatory markers by ICS(50%), reduction in rescue medication in both groups(100%).ICS alone (3 studies): good control of asthma including exercise asthma(66.7%).This Research concluded that the prophylactic inhaled steroids are more effective compared to placebo, mast cell stabilizer drugs and leukotriene receptor antagonist. ICS improving both clinical and laboratory outcomes in childhood asthma.&#x0D;

Contribution of monocyte and macrophage extracellular traps to neutrophilic airway inflammation in severe asthma

BackgroundIncreased blood/sputum neutrophil counts are related to poor clinical outcomes of severe asthma (SA), where we hypothesized that classical monocytes (CMs)/CM-derived macrophages (Mφ) are involved. We aimed to elucidate the mechanisms of how CMs/Mφ induce the activation of neutrophils/innate lymphoid cells (ILCs) in SA. MethodsSerum levels of monocyte chemoattractant protein-1 (MCP-1) and soluble suppression of tumorigenicity 2 (sST2) were measured from 39 patients with SA and 98 those with nonsevere asthma (NSA). CMs/Mφ were isolated from patients with SA (n = 19) and those with NSA (n = 18) and treated with LPS/interferon-gamma. Monocyte/M1Mφ extracellular traps (MoETs/M1ETs) were evaluated by western blotting, immunofluorescence, and PicoGreen assay. The effects of MoETs/M1ETs on neutrophils, airway epithelial cells (AECs), ILC1, and ILC3 were assessed in vitro and in vivo. ResultsThe SA group had significantly higher CM counts with increased migration as well as higher levels of serum MCP-1/sST2 than the NSA group. Moreover, the SA group had significantly greater production of MoETs/M1ETs (from CMs/M1Mφ) than the NSA group. The levels of MoETs/M1ETs were positively correlated with blood neutrophils and serum levels of MCP-1/sST2, but negatively correlated with FEV1%. In vitro/in vivo studies demonstrated that MoETs/M1ETs could activate AECs, neutrophils, ILC1, and ILC3 by increased migration as well as proinflammatory cytokine production. ConclusionsCM/Mφ-derived MoETs/M1ETs could contribute to asthma severity by enhancing neutrophilic airway inflammation in SA, where modulating CMs/Mφ may be a potential therapeutic option.

Intrauterine Smoke Exposure, microRNA Expression during Human Lung Development, and Childhood Asthma.

Intrauterine smoke (IUS) exposure during early childhood has been associated with a number of negative health consequences, including reduced lung function and asthma susceptibility. The biological mechanisms underlying these associations have not been established. MicroRNAs regulate the expression of numerous genes involved in lung development. Thus, investigation of the impact of IUS on miRNA expression during human lung development may elucidate the impact of IUS on post-natal respiratory outcomes. We sought to investigate the effect of IUS exposure on miRNA expression during early lung development. We hypothesized that miRNA-mRNA networks are dysregulated by IUS during human lung development and that these miRNAs may be associated with future risk of asthma and allergy. Human fetal lung samples from a prenatal tissue retrieval program were tested for differential miRNA expression with IUS exposure (measured using placental cotinine concentration). RNA was extracted and miRNA-sequencing was performed. We performed differential expression using IUS exposure, with covariate adjustment. We also considered the above model with an additional sex-by-IUS interaction term, allowing IUS effects to differ by male and female samples. Using paired gene expression profiles, we created sex-stratified miRNA-mRNA correlation networks predictive of IUS using DIABLO. We additionally evaluated whether miRNAs were associated with asthma and allergy outcomes in a cohort of childhood asthma. We profiled pseudoglandular lung miRNA in n = 298 samples, 139 (47%) of which had evidence of IUS exposure. Of 515 miRNAs, 25 were significantly associated with intrauterine smoke exposure (q-value < 0.10). The IUS associated miRNAs were correlated with well-known asthma genes (e.g., ORM1-Like Protein 3, ORDML3) and enriched in disease-relevant pathways (oxidative stress). Eleven IUS-miRNAs were also correlated with clinical measures (e.g., Immunoglobulin E andlungfunction) in children with asthma, further supporting their likely disease relevance. Lastly, we found substantial differences in IUS effects by sex, finding 95 significant IUS-miRNAs in male samples, but only four miRNAs in female samples. The miRNA-mRNA correlation networks were predictive of IUS (AUC = 0.78 in males and 0.86 in females) and suggested that IUS-miRNAs are involved in regulation of disease-relevant genes (e.g., A disintegrin and metalloproteinase domain 19 (ADAM19), LBH regulator of WNT signaling (LBH)) and sex hormone signaling (Coactivator associated methyltransferase 1(CARM1)). Our study demonstrated differential expression of miRNAs by IUS during early prenatal human lung development, which may be modified by sex. Based on their gene targets and correlation to clinical asthma and atopy outcomes, these IUS-miRNAs may be relevant for subsequent allergy and asthma risk. Our study provides insight into the impact of IUS in human fetal lung transcriptional networks and on the developmental origins of asthma and allergic disorders.

Physical training in adults with asthma: An integrative approach on strategies, mechanisms, and benefits.

Asthma is a chronic airway disease characterized by airflow limitation and respiratory symptoms associated with chronic airway and systemic inflammation, bronchial hyperreactivity (BHR), and exercise-induced bronchoconstriction (EIB). Asthma is a heterogeneous disease classified according to distinct airway and systemic inflammation. Patients commonly present with several comorbidities, including anxiety, depression, poor sleep quality, and reduced physical activity levels. Individuals with moderate to severe asthma often have more symptoms and difficulty achieving adequate clinical control, which is associated with poor quality of life, despite proper pharmacological treatment. Physical training has been proposed as an adjunctive therapy for asthma. Initially, it was suggested that the effect of physical training might be attributed to the improved oxidative capacity and reduced production of exercise metabolites. However, in the last decade, there has been evidence that aerobic physical training promotes anti-inflammatory effects in asthma patients. Physical training improves BHR and EIB, asthma symptoms, clinical control, anxiety, and depression levels, sleep quality, lung function, exercise capacity, and dyspnea perception. Furthermore, physical training reduces medication consumption. The most commonly used exercise strategies are moderate aerobic and breathing exercises; however, other techniques, such as high-intensity interval training, have shown promising effects. In the present study, we reviewed the strategies and beneficial effects of exercise on clinical and pathophysiological asthma outcomes.

The impact of unsupervised and unconsented switch of inhalers in patients with controlled asthma - A targeted literature review.

Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate) and a long-acting β2 agonist (salmeterol xinafoate) are indicated as maintenance treatments for patients with asthma and/or for selected patients with chronic obstructive pulmonary disease. The emergence of generic equivalents to branded inhalers is expected to offer economic edge/savings; however, some may argue that cost advantages offered by generic inhalers may be offset by worsening outcomes due to improper inhaler use, reduced adherence, and consequently worse disease control. To understand how unsupervised and unconsented switch of dry-powder inhalers and/or metered-dose inhalers affects clinical and humanistic outcomes in asthma, comprehensive searches of Embase and MEDLINE were conducted to identify research articles published in the English language since 2011. Patients with asthma of any age who underwent an unsupervised and unconsented switch from an ICS/long-acting β2 agonist to another (brand-to-generic or brand-to-brand) for non-medical reasons were the target of this research. Relevant outcomes included asthma control, medication adherence, and healthcare resource utilization. In total, 11 studies were identified for review (ten non-interventional and one post hoc); cohorts ranged from 19 to 42,553 patients. Six studies indicated that unsupervised and unconsented inhaler switch had a negative impact on asthma control; six studies indicated reduced medication adherence post-switching; and five studies reporting healthcare resource utilization showed it was unchanged or increased post-switching. Findings from this targeted review support concerns that unsupervised and unconsented inhaler switch has a largely negative impact on asthma-associated outcomes. Additional studies are warranted to further explore unsupervised and unconsented switch in asthma.

Dyslipidemia Is Associated With Worse Asthma Clinical Outcomes: A Prospective Cohort Study

Dyslipidemia has been widely documented to be associated with cardiovascular disease, and recent studies have found an association with asthma prevalence. However, longitudinal studies investigating the relationships between dyslipidemia, asthma phenotypes, and future asthma exacerbations (AEs) are lacking. To investigate the relationships between dyslipidemia, asthma phenotypes, and AEs. This study used an observational cohort study design with a 12-month follow-up. All subjects underwent serum lipid measurement, and they were then classified into 2 groups: the normal-lipidemia group and the dyslipidemia group. Demographic and clinical information and details regarding pulmonary function and asthma phenotypes at baseline were collected. All patients were followed up regularly to assess AEs. Associations of dyslipidemia with airway obstruction and asthma phenotypes were assessed at baseline, whereas dyslipidemia and AEs were assessed longitudinally. A total of 477 patients with asthma were consecutively enrolled in this study. At baseline, the dyslipidemia group (n= 218) had a higher proportion of uncontrolled asthma, defined by the 6-item Asthma Control Questionnaire score (≥1.5). Furthermore, dyslipidemia was associated with severe asthma, nonallergic asthma, asthma with fixed airflow limitation, and older adult asthma phenotypes at baseline. In addition, dyslipidemia was associated with increased frequencies of severe AEs and moderate to severe AEs during the 12-month follow-up. In sensitivity analyses, after excluding the patients who were receiving statins, results did not differ significantly from those of the main analysis. We identified the clinical relevance of dyslipidemia, which is associated with specific asthma phenotypes and increased AEs, independent of other components of metabolic syndrome. These findings highlight the importance of considering dyslipidemia as an "extrapulmonary trait" in asthma management.