Journal of Asthma最新文献

Objective: To investigate whether tapering of inhaled corticosteroids (ICSs) is non-inferior to standard of care (SoC) in asthma patients with a stable type 2 (T2)-low inflammatory profile, generally considered less responsive to ICS therapy, and to describe symptom and biomarker trajectories during tapering.

Methods: This randomized, controlled, open-label multicenter trial conducted across specialist centers between 2022 and 2024 recruited adult asthma patients with persistently low T2 biomarkers, defined as blood eosinophils <0.15 × 10⁹/L, fractional exhaled nitric oxide (FeNO) <25 ppb, and non-allergic phenotype. Patients' adherent to medium- or high-dose ICS were randomized 1:1 to either ICS tapering (50% reduction at randomization and withdrawal after 8 weeks) or continued SoC. The primary endpoint was change in Asthma Control Questionnaire (ACQ) score at 16 weeks. Secondary endpoints included changes in blood and sputum eosinophils, FeNO, periostin, and lung function.

Results: Recruitment proved challenging as only 20 of 2766 screened patients met eligibility criteria, leading to early study termination. Median ACQ remained stable in the tapering group (0 [-0.14; 0.5]) and improved modestly in the SoC group (-0.44 [-0.9; -0.11]; p = 0.211). FeNO (p = 0.038) and periostin (p = 0.031) increased with tapering but remained within the T2 low range. Minimal changes were observed in blood eosinophils (p = 0.3) and FEV₁ (p = 0.7).

Conclusions: Premature trial termination due to recruitment challenges reflects the rarity of stable T2-low asthma. ICS tapering was not associated with greater symptom deterioration compared to SoC, although non-inferiority was not demonstrated.

Objective: To describe the use of guideline-recommended specialist care (i.e., pulmonology, allergy) among historically marginalized children with uncontrolled asthma and explore factors associated with specialist care use.

Methods: We analyzed baseline data from the Telemedicine Enhanced Asthma Management - Uniting Providers (TEAM-UP) trial in Rochester, NY (2018-2023). Caregivers reported on their child's demographics, specialist care utilization/perceptions, and recent asthma symptoms. We conducted bivariate and multivariate analyses to compare specialist care use with demographics, asthma outcomes, primary care physician (PCP) referrals, and caregiver beliefs regarding specialist care.

Results: Among the 325 enrolled children ages 4-12 years (participation rate 62%; 60% male, 35% Hispanic, 58% Black, 80% public insurance), 37% had ever been seen by a specialist and 16% saw a specialist in the prior year. Compared to children who did not see a specialist in the prior year, those who received specialist care were younger, and more were Hispanic, lived in smoke-free homes, had married caregivers, and had household incomes of at or >$35,000. While PCP referrals increased the likelihood of children receiving specialist care, only 23% of children were referred to a specialist by their PCP. Among those not seen by a specialist, 38% reported allergic rhinitis, 42% had smoke exposure within the home, and 81% of caregivers felt specialist care would be helpful for their child.

Conclusions: This study emphasizes inadequate use of asthma specialist care among marginalized communities, and how PCP referrals may improve the receipt of guideline-recommended specialist care for vulnerable youth with poorly controlled asthma.

Objective: Asthma demonstrates pronounced sex-based disparities, with adult females exhibiting a disproportionately higher disease burden. Although aberrant lipid metabolic profiles have been mechanistically linked to asthma pathogenesis, the specific association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and asthma risk in women remains unclear. This study aims to investigate the relationship between NHHR and asthma risk in middle-aged women using a nationally representative U.S. population.

Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. A variety of statistical methods, such as multivariable logistic regression models, smoothed curve fitting, threshold effect analyses, and subgroup analyses, were used to explore the relationship between NHHR and asthma risk.

Results: A total of 7337 participants aged 30-65 years were included, with an asthma prevalence of 16.82%. After full adjustment for demographic, socioeconomic, lifestyle, and clinical factors, higher NHHR remained positively associated with asthma risk (OR = 1.26, 95% CI: 1.01-1.58). Smooth curve fitting revealed a nonlinear relationship with a threshold inflection point at Log10(NHHR) = 0.07 (corresponding to NHHR ≈ 1.17). Above this threshold, asthma risk increased significantly (OR = 1.78, 95% CI: 1.24-2.54). Subgroup analyses indicated a significant interaction with education level, showing stronger associations among women with lower educational attainment.

Conclusions: Elevated NHHR is independently and nonlinearly associated with asthma risk in middle-aged women. The findings suggest that dysregulated lipid metabolism may contribute to asthma susceptibility, highlighting NHHR as a potential biomarker for metabolic-inflammatory crosstalk and in women's respiratory health.

Background: Asthma is a common chronic respiratory disease, cardiovascular disease (CVD) mortality constitutes a major public health concern. At present, no personalized tools are available to accurately estimate CVD mortality risk in this population. Accordingly, a machine learning model was developed to predict incident CVD mortality of asthma.

Methods: Data were extracted from NHANES (2007-2012). Predictors were selected by LASSO and multivariable Cox regression. Discrimination and calibration were quantified with ROC curves and calibration curves, nomogram and web calculator were subsequently deployed. Incremental predictive value relative to ASCVD risk and Framingham risk scores were assessed with the integrated discrimination improvement and net reclassification improvement. Six machine learning algorithms were trained, and feature importance of the optimal model was interpreted with SHAP values.

Results: Among 2,033 adults participants with asthma, with mean age 44 years, and they comprised 834 males (41.02%) and 1199 females (58.98%). Twelve variables (age, sex, smoking, hypertension, diabetes, CKD, SBP, LYM, UA, K, FENO, and PEF) were retained as predictors of CVD mortality. Calibration was stable across training sets (C-index = 0.863) and validation sets (C-index = 0.832). The pulmonary function test augmented NHANES model outperformed both ASCVD risk and Framingham risk scores. RF and XGB model achieved the highest discrimination.

Conclusion: A machine learning model integrating routine clinical and pulmonary function test indices was developed. The model enables accurate estimation of long term CVD mortality risk with asthma, facilitating early identification of high risk individuals and informing personalized preventive strategies.

Objective: This study aimed to measure the impact of repeated counseling on asthma control and inhaler technique using pressurized metered-dose inhaler (pMDI) alone and in combination with pMDI PLUS^® (cardboard-based spacer) or AeroChamber2go^® in adult asthma patients.

Methods: This is a prospective randomized clinical trial in which a cohort of 300 asthma patients was randomly allocated into three equal groups (n = 100): (1) pMDI alone, (2) pMDI + MDI PLUS^®, and (3) pMDI + AeroChamber2go^®. The patient groups were interviewed to assess the inhalation technique of the three devices, in parallel, upon three monthly separate visits. At baseline and during two subsequent monthly visits, each group received three standardized training sessions. Before each session, patients performed the inhalation steps with their assigned device, and the number of technical errors was recorded. Lung function (Forced Expiratory Volume in one second (FEV₁) % of predicted, Peak Expiratory Flow (PEF) % of predicted) and Asthma Control Test (ACT) scores were also assessed.

Results: At the first visit, MDI PLUS^® and AeroChamber2go^® groups made significantly fewer inhalation errors than the pMDI alone group (p = 0.04 and p = 0.041, respectively). Error rates with pMDI alone only decreased significantly by the third visit (p = 0.04). Throughout all visits, MDI PLUS^® consistently showed fewer errors than AeroChamber2go^®, although this difference did not reach statistical significance (p > 0.05). Regarding clinical outcomes, both spacer groups experienced significant, visit-to-visit improvements in FEV₁% of predicted, PEF% of predicted, and ACT scores (all p < 0.05 between visit 1 and 2 and between visit 2 and 3). In contrast, the pMDI alone group showed no significant change between visits 1 and 2, with statistically significant improvement only by visit 3 (FEV₁, p = 0.04; PEF, p = 0.03; ACT, p = 0.04).

Conclusion: Counseling asthmatic patients with either spacer has significantly reduced inhalation errors and provided greater and earlier improvements in terms of lung function and asthma control compared to pMDI alone.

Objective: Airway inflammation and remodeling are key pathological features of bronchial asthma, yet the therapeutic potential and mechanisms of Tanshinone IIA (Tan IIA) remain incompletely understood. This study aimed to evaluate the effects of Tan IIA on airway inflammation and remodeling and to elucidate the underlying signaling mechanisms.

Methods: A chronic bronchial asthma mouse model was established and complemented by in vitro studies using human bronchial epithelial cells (16HBEs) and human tracheal smooth muscle cells (HTSMCs). In bronchoalveolar lavage fluid (BALF), inflammatory cell counts and relevant mediators were assessed. Histological analyses were performed to evaluate airway inflammatory injury and remodeling changes. Mechanistic investigations examined p38 and AKT phosphorylation and the nuclear translocation of NF-κB and HIF-1α in vivo, with validation in cell-based experiments.

Results: Tan IIA reduced Th2 cytokines (IL-4, IL-5, and IL-13), remodeling-associated factors (VEGF and TGF-β1), and the numbers of eosinophils, neutrophils, and lymphocytes in BALF. Histopathological assessment showed that Tan IIA alleviated inflammatory cell infiltration, epithelial damage, basement membrane thickening, goblet cell hyperplasia, mucus hypersecretion, and subepithelial collagen deposition. Mechanistically, Tan IIA decreased phosphorylated p38 (p-p38) and phosphorylated AKT (p-AKT) and inhibited the nuclear translocation of NF-κB and HIF-1α in vivo. These findings were corroborated in vitro: in 16HBEs, Tan IIA suppressed p-p38 activation and NF-κB nuclear translocation, whereas in HTSMCs, it reduced p-AKT levels and inhibited HIF-1α nuclear translocation.

Conclusion: Tan IIA attenuates airway inflammation and remodeling by inhibiting the p38/NF-κB and AKT/HIF-1α signaling pathways, supporting Tan IIA as a promising therapeutic candidate for bronchial asthma.

Objective: Differentiating between asthma and chronic obstructive pulmonary disease (COPD) and treating them correctly is challenging because their symptoms overlap and current diagnostic methods are inadequate. We explored the potential of integrating breath metabolomics with sputum inflammatory phenotyping to enhance the discrimination and characterization of respiratory diseases.

Methods: Exhaled breath samples were gathered from 74 participants (35 with asthma, 39 with COPD), and sputum samples were examined for eosinophil and neutrophil counts. Orthogonal partial least squares-discriminant analysis (OPLS-DA), logistic regression, and principal component analysis (PCA) were used for the identification of significant volatile organic compounds (VOCs) that discriminate between the diseases, and to determine their relationship to disease state and inflammatory classifications.

Results: Breath metabolomics effectively distinct asthma from COPD with 93.2% accuracy, identifying 10 important VOC biomarkers. Significantly, predicting sputum eosinophilia and neutrophilia phenotypes using established thresholds was more accurate (80.6%-90.5%, AUROC 0.67-0.91) compared to directly differentiating the diseases, where each inflammatory subtype presented its own VOC profile. Specific biomarkers, such as allyl methyl sulfide, epizonarene, and camphor, were identified as potential indicators of disease status and inflammatory subtypes.

Conclusion: Using breath metabolomics in conjunction with sputum inflammatory phenotyping shows promise in effectively distinguishing between asthma and COPD, as well as identifying inflammatory subtypes, which can aid in creating personalized treatment strategies.

Objective: Caregivers of children with a chronic illness often experience stress that can impact their child's health and influence the parent-child relationship dynamic through changes in communication patterns. Within a pediatric asthma sample, we examined the associations between medical factors and caregiver stress on parent-child communication patterns and youth quality of life (QOL).

Methods: Youth with asthma (n = 70; M_age = 13.99; 43% female) and their caregivers (94% female; 46% White) were recruited from a pediatric pulmonary clinic. Hierarchical regression models examined the unique contributions of medical factors and caregiver stress (Pediatric Inventory for Parents, PIP) on caregiver-child communication patterns (Revised Family Communication Pattern Instrument, RFCP; openness vs. conforming to family ideals) and youth QOL (Pediatric Asthma Quality of Life Questionnaire, PAQLQ).

Results: On a scale of 42-210, in which higher scores indicate greater frequency or difficulty of problems contributing to caregiver stress, caregivers reported an average frequency score of 83.91 (SD = 30.226) and an average difficulty score of 79.00 (SD = 32.767). More emergency room visits in the past 12 months (B = .327, p = 0.006) were related to greater endorsement of parent-child communication conformity orientation, explaining 21.1% of variance, F(3,61) = 5.45, p = 0.002; caregiving stress was only associated at the bivariate level. Higher caregiving stress difficulty (B = -0.389, p = 0.001) was related to lower youth QOL, explaining 17.0% of variance, F(2,64) = 6.55, p = 0.003.

Conclusions: Caregivers of youth with asthma reported low-moderate caregiving stress in both frequency and difficulty of problems faced. Nevertheless, caregiving stress difficulty was a predictor of their child's QOL above and beyond medical factors. Healthcare providers should screen for caregiving stress and continue to monitor caregiver well-being throughout the illness trajectory.