Mucus Plugging Research Articles

Comparison of thromboelastographic profiles and clinical characteristics in children with severe Mycoplasma pneumoniae pneumonia

BackgroundThis study aimed to compare Thromboelastographic (TEG) profiles and clinical characteristics between severe Mycoplasma pneumoniae (MP) pneumonia patients with normal and abnormal TEG parameters.MethodsThe clinical data of 133 children with severe MP pneumonia were retrospectively analyzed. Patients were divided into normal (n = 76) and abnormal (n = 57) TEG groups. Demographic characteristics, clinical manifestations, laboratory findings, imaging features, bronchoscopy results, treatment, complications, and outcomes were compared between groups.ResultsThe abnormal TEG group (42.9%) had longer fever duration (median: 8.5 vs. 7.0 days, P < 0.001) and hospital stay (median: 11.5 vs. 10.0 days, P = 0.003). They also showed higher levels of C-reactive protein (median: 30.2 vs. 20.1 mg/L, P < 0.001), lactate dehydrogenase (median: 334.5 vs. 276.0 U/L, P = 0.001), and D-dimer (median: 1.2 vs. 0.5 μg/ml, P < 0.001). HRCT revealed more lobar consolidation or multilobar involvement (36.8% vs. 18.4%, P = 0.016), and bronchoscopy showed more mucous plug obstruction (28.1% vs. 10.5%, P = 0.008) in the abnormal TEG group. TEG parameters indicated a hypercoagulable state with shorter R time (P < 0.001), shorter K time (P < 0.001), and higher MA (P = 0.003). The abnormal TEG group had higher incidences of coagulopathy (P < 0.001), cardiac involvement (elevated cardiac enzymes: 36.8% vs. 17.1%, P = 0.009; pericardial effusion: 10.5% vs. 1.3%, P = 0.017), and plastic bronchitis (P = 0.006). They also required longer azithromycin courses (median: 15 vs. 14 days, P = 0.026).ConclusionChildren with severe MP pneumonia and abnormal TEG profiles have more severe clinical manifestations, higher inflammatory markers, more extensive lung involvement, and a higher incidence of complications. TEG may help identify high-risk patients and guide management in severe MP pneumonia.

Mucus Plug Score predicts clinical and pulmonary function response to biologic therapy in patients with severe Asthma.

Mucus plugging has been identified as an important feature of severe asthma contributing to airway obstruction and disease severity. Recently, improvement of mucus plugging has been found upon treatment with several biologic therapies. We aimed to analyze associations of baseline characteristic with mucus plugging score (MPS) and asked whether MPS at baseline predicts the clinical and functional response to biologic treatment in patients with severe asthma. We retrospectively analyzed biologic-naïve patients with a suitable CT scan available at baseline. We calculated the MPS and analyzed correlations with baseline parameters and improvements of biomarkers, pulmonary function and clinical parameters after 4 months of biologic therapy. We included n=113 patients in the baseline cohort, hereof n=101 patients with sufficient data after 4-months of biologic therapy for the follow-up analysis. CT showed mucus plugging in 77% of patients with a median MPS of 4. Multivariate regression analysis showed correlation of MPS with lower FEV1 (rho= -0.24, p=0.009) and DLCO (rho=-0.26 , p= 0.01), and higher FeNO (rho=0.36 p=0.0003) at baseline. Patients received treatment with anti-IgE (8.8%), anti-IL5 (27.4%), anti-IL5R (37.2%), anti-IL4R (25.7%) and anti-TSLP (0,9%) in clinical routine. Baseline MPS correlated with improvements of FEV1 (beta=0.72; p=0.01) and ACT (beta= 0.24; p= 0.001) in multivariate regression analysis. Our study suggests that higher MPS correlates with worse pulmonary function at baseline, but also predicts a larger clinical and pulmonary function response to biologic therapies in severe asthma.

Correlation of Aspergillus fumigatus Sensitization with Mucus Plugging in COPD.

Both Aspergillus fumigatus sensitization and mucus plugs are associated with poor clinical outcomes in COPD. However, little is known about the association between Aspergillus hypersensitivity and mucus plugging in patients with COPD. We retrospectively enrolled COPD patients who had visited Peking University Third Hospital and received measurement of the Aspergillus Fumigatus specific IgE (Af sIgE) from Oct 1, 2018 to Sep 30, 2023. The clinical, laboratory, and chest CT features were analyzed, with mucus plugging evaluation using the bronchopulmonary segment-based scoring system. Comparison was performed between COPD patients with and without Aspergillus hypersensitivity (AH). Among the 378 COPD patients with measurement of Af sIgE, 29 (7.7%) were classified as having AH (Af sIgE>0.35KU/L). By propensity score matching (1:2), 58 patients without AH were included for comparison. Patients with AH had lower FEV1%pred (P=0.008) and FEV1/FVC (%) (P=0.023), and were more likely to have a blood eosinophil count exceeding 300/µL and higher white blood cell and neutrophil counts. The prevalence of luminal plugging on chest CT in subjects with AH was 58.6%, compared to 31.0% in those without AH (P=0.013). Multivariate regression analyses showed that Af sIgE more than 0.70 KU/L and blood neutrophil count were associated with mucus plugging. In patients with COPD, Aspergillus sensitization was associated with lower lung function and mucus plugging on chest CT.

Application of low-dose FDG-PET/MRI for quantification of lung changes in pediatric patients with cystic fibrosis: a new inflammatory index.

Clinical severity and progression of lung disease in cystic fibrosis (CF) are significantly influenced by the degree of lung inflammation. Non-invasive quantitative diagnostic tools are desirable to differentiate structural and inflammatory lung changes in order to help prevent chronic airway disease. This might also be helpful for the evaluation of longitudinal effects of novel therapeutics. Therefore, the present study assesses the quantification of inflammatory lung changes using positron emission tomography/magnetic resonance imaging (PET/MRI) of the lung in children and adolescents with CF and evaluates the possible impact of PET/MRI on individualized therapy management. This monocentric, retrospective cohort study included 19 PET/MRI of the lung performed between 2014 and 2021 in 11 patients (16±4.5 years, 8-22 years; 7 females). PET acquisition was performed at least 20 minutes after i.v. application of a weight-adjusted dose of fluor-18-fluorodeoxyglucose (18F-FDG) of 1 MBq/kgBW (mean effective dose, 1.3±0.4 mSv). Lesions of increased uptake were quantified based on standardized uptake values (SUV) and compared to background activity, liver and blood pool. Pulmonary changes were assessed using the established magnetic resonance imaging-CF (MR-CF) score and correlated to inflammatory lesions. Results were correlated to changes in therapy (initiation, modification or discontinuation of therapy after baseline-PET/MRI) based on the electronic medical records. Uptake was highly increased in 5 cases, moderate in 4 cases, low in 7 cases, no uptake in 3 cases. Most MR-CF score points were assigned to peribronchitis (23%) and air trapping (23%). Metabolically increased lesions were mainly interpreted as consolidations (59%; P<0.001) and mucus plugging (19%, P=0.024). There was a decrease in mean number and volumes of inflammatory lesions (P=0.016 each) and MR-CF score (P=0.047) between baseline and follow-up. After PET/MRI, therapy changed in 18 cases (95%; new medication: 58%, n=11; termination of therapy: 16%, n=3; modification of therapy: 21%, n=4). In selected cases, pulmonary FDG-PET/MRI can help guide therapeutic decision-making and provide complementary information on CF-related lung changes to conventional MRI at a low radiation exposure.

Asthma Biologics Across the T2 Spectrum of Inflammation in Severe Asthma: Biomarkers and Mechanism of Action.

Airway inflammation, a hallmark feature of asthma, drives many canonical features of the disease, including airflow limitation, mucus plugging, airway remodeling, and hyperresponsiveness. The T2 inflammatory paradigm is firmly established as the dominant mechanism of asthma pathogenesis, largely due to the success of inhaled corticosteroids and biologic therapies targeting components of the T2 pathway, including IL-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP). However, up to 30% of patients may lack signatures of meaningful T2 inflammation (ie, T2 low). In T2-low asthma patients, T2 inflammation may be masked due to anti-inflammatory treatments or may be highly variable depending on exposure to common asthma triggers such as allergens, respiratory infections, and smoke or pollution. The epithelium and epithelial cytokines (TSLP, IL-33) are increasingly recognized as upstream drivers of canonical T2 pathways and as modulators of various effector cells, including mast cells, eosinophils, and neutrophils, which impact the pathological manifestations of airway smooth muscle hypertrophy, hypercontractility, and airway hyperresponsiveness. Approved biologics for severe asthma target several distinct mechanisms of action, leading to differential effects on the spectrum of T2 inflammation, inflammatory biomarkers, and treatment efficacy (reducing asthma exacerbations, improving lung function, and diminishing symptoms). The approved anti-asthma biologics primarily target T2 immune pathways, with little evidence suggesting a benefit of targeting non-T2 asthma-associated mediators. Indeed, many negative results challenge current assumptions about the etiology of non-T2 asthma and raise doubts about the viability of targeting popular alternative inflammatory pathways, such as T17. Novel data have emerged from the use of biologics to treat various inflammatory mediators and have furthered our understanding of pathogenic mechanisms that drive asthma. This review discusses inflammatory pathways that contribute to asthma, quantitatively outlines effects of available biologics on biomarkers, and summarizes data and challenges from clinical trials that address non-T2 mechanisms of asthma.

Family Caregiver Knowledge in the Outpatient Management of Pediatric Tracheostomy-Related Emergencies.

Tracheostomy-related emergencies (TREs) contribute significantly to preventable mortality. The retention of caregiver knowledge and skills acquired through simulation-based training (SBT) is unknown. This study aimed to assess the management of TREs by caregivers who did and did not receive SBT. A questionnaire containing 3 TRE scenarios and frequency of outpatient TREs was administered to 52 caregivers of children with tracheostomies; 34 caregivers had completed SBT. Most caregivers (80%) reported ≥1 TRE since discharge. Only 46% of caregivers answered all 3 TRE questions correctly. No differences were observed in correct responses for accidental decannulation (p = .16), oxygen desaturation (p = .84), and mucus plugging (p = .16) based on the completion of SBT. There were no differences between duration since SBT completion and correct responses for all 3 TRE questions. Caregivers showed knowledge deficiencies in TRE management regardless of SBT completion or duration since SBT. Periodic reassessment of knowledge may create targeted re-education opportunities for TRE management.

Outpatient Ductal Steroid Irrigations as an Adjuvant Treatment to Sialendoscopy in Recurrent Inflammatory Obstructive Sialadenitis

The aim of this study is to retrospectively investigate the effectiveness of outpatient ductal steroid irrigations (DSIs) as an adjuvant treatment in recurrent inflammatory obstructive sialadenitis (RIOS). A retrospective chart review of prospectively recruited RIOS patients was randomly assigned to group A (i.e., interventional sialendoscopy) or group B (i.e., interventional sialendoscopy with outpatient DSIs). The statistical analysis detected any postoperative difference between groups in terms of the number and severity (attested by 0–10 VAS pain) of episodes of swelling. Interventional sialendoscopy and DSIs were effective and well tolerated in all 122 patients, and a significantly reduced number of salivary gland swelling episodes (p-value = 0.01) was documented in group B compared to group A at any follow-up assessment. When the specific aetiology was considered, repeated DSIs were more effective than interventional sialendoscopy alone in patients with type 1 or 3 stenoses and in those without mucous plugs. Our results confirm the safety and effectiveness of interventional sialendoscopy (both as a single-modality and a multimodal approach) in a large series of adult patients with RIOS at short-, medium-, and long-term analyses. The superiority of a combined therapeutic protocol, with a positive effect still detectable 12 months after the end of the treatment, was attested as well.

Assessing the Safety and Efficacy of Self-Expanding Metallic Y Stents in a Community Medicine Setting

Self-Expanding Metallic (SEM) Y stents are a newer form of stent that is gaining popularity outside the USA, but still has limited data, especially in a community medicine setting. This study analyzed efficacy and complication rates in 14 patients who had a SEM Y stent placed between August 2022 and June 2024 at Harris Methodist Hospital in Fort Worth, Texas for either central airway obstruction (CAO) or fistulae. Of the 14 patients, 11 were requiring supplemental oxygen or mechanical ventilation prior to stent placement. Post-stenting 42.9% had decreased oxygen requirements, 21.4% unchanged, 14.3% increased, and 21.4% remained on room air. Complications included mucus plugging (42.9%), infection (35.7%), and granulation tissue (14.3%). There was no statistically significant correlation between gender/age and complications (p = 0.879/0.490, respectively). Complication rates were similar when compared to silicone Y stents based on literature review. In conclusion, SEM Y stents are a safe and effective alternative stent intended for palliative treatment with similar success and complications that can be easily and effectively implemented in a community hospital, with the added benefit of being able to be placed with flexible bronchoscopy.

Chest CT assess the impact of omalizumab treatment on airway remodeling in refractory asthma.

BackgroundTo evaluate the benefits of omalizumab treatment in patients through real-world follow-up and assess the impact of omalizumab treatment on airway remodeling using chest CT. MethodsThis is a single-center prospective, observational study included Chinese patients with refractory asthma who received omalizumab treatment from May 2021 to December 2022. We collected real-world clinical data, including their hospitalization information, pulmonary function, FENO, laboratory assessment, ACT scores, chest CT at baseline and every follow-up month. A comparison was made between the pre-treatment and post-treatment laboratory indicators, pulmonary function, airway parameters, and mucous plug scores under chest CT. ResultsThis study included a total of 61 patients with refractory asthma treated with omalizumab. The study found that: ①regardless of whether the treatment lasted for a full four months or not, it significantly improved patient asthma control scores and reduced hospitalization costs and length of stay (p<0.05). ②After four months of treatment, pulmonary ventilation function examination revealed significant improvements (p<0.05) in MEF75, MEF50, MEF75/25, PEF, and FEV1/FVC. ③After four months of omalizumab treatment, the ratio of wall thickness and outer radius (T/D) and wall area percentage (WA%) of the bronchial wall decreased significantly (p<0.05). ④After medication, the expression of airway mucous plugs decreased. ConclusionsOmalizumab treatment can reduce airway wall thickness, decrease the percentage of airway wall area, and the expression of airway mucous plugs, thereby improving airflow limitation. Utilizing chest CT provides a novel and intuitive assessment of the efficacy of omalizumab treatment. Trial registrationThis study was registered in Chinese Clinical Trial Registry, the number is ChiCTR2100046343.

Establishment of a survival rabbit model for laryngotracheal stenosis: A prospective randomized study.

To develop a reproducible survival rabbit model for laryngotracheal stenosis (LTS). Seventy New Zealand white (NZW) rabbits were randomly divided into experimental groups (n = 30) and a control group (n = 40). In experimental groups, a nylon brush was inserted retrograde from the tracheotomy through the subglottis and rotated until a full layer circumferential mucosal injury to cartilage exposure, assisted by fiberoptic laryngoscopy (FOL) visualization. Experimental group 1 (n = 10), rotated 10 times; group 2 (n = 20), rotated 20 times. The control group underwent tracheotomy only without nylon brush scraping. The rabbits underwent FOL at 1st, 4th, 8th, and 12th week postinjury respectively to observe the formation of LTS. They were euthanized and the larynxes and tracheas were subjected to gross and histopathological examination at 12 weeks postinjury. The control group all survived, while five cases in experimental groups died from LTS and/or mucous plug. Histological observation showed that the control group had intact laryngotracheal mucosal epithelium without any stenosis; the experimental groups showed proliferation of fibroblasts and thickening of collagen fibers. The mean stenosis in control group was 9.31 ± 0.98%, while that in experimental group 1 was 32.78 ± 7.07% and 58.25 ± 8.96% in experimental group 2. The difference between the three groups was statistically significant (χ 2 = 47.98, p < .05). We successfully developed a reproducible survival rabbit model for LTS using a nylon brush through FOL visualization combined with tracheostomy. This model can provide a mature and stable animal model for the exploration of wound-healing pathophysiology and the effect of interventions. NA.

Mucus plugging, disease severity, and sputum myeloperoxidase concentration in bronchiectasis

BackgroundBronchiectasis is characterized by impaired mucociliary clearance, leading to persistent mucus accumulation, known as mucus plugging (MP). Myeloperoxidase (MPO) is a key molecule that activates neutrophilic inflammation during bronchiectasis, leading to disease progression. However, whether sputum MPO concentration is an independent factor associated with MP remains unclear.MethodsWe retrospectively evaluated 78 patients with bronchiectasis at Chungbuk National University Hospital between June 2022 and April 2023. According to the extent of MP in computed tomography of the chest, participants were divided into high MP (MP in ≥ 10 bronchopulmonary segments) and low MP (MP in ≤ 9 bronchopulmonary segments) groups. We evaluated whether sputum MPO concentration is independently associated with MP using multivariable adjusted logistic regression analyses.ResultsThere were 59 (75.6%) and 19 (24.4%) participants in the low and high MP groups, respectively. Compared with the low MP group, the high MP group had significantly higher disease severity, as measured by the modified Reiff score (p&lt;0.001) and FACED score (p=0.003). Sputum MPO concentration was significantly correlated with the extent of MP (r=0.313, p=0.009). In addition, sputum MPO concentration (adjusted odds ratio=1.60, 95% confidence interval: 1.06–2.42) was independently associated with a high extent of MP even after adjusting for potential confounders.ConclusionsSputum MPO concentration was associated with a high degree of MP, suggesting a potential role of MPO in the pathogenesis of mucus plugging.

Real-world improvement in ultra-low dose thoracic CT scores, systemic inflammatory markers, and patients reported outcome measures post elexacaftor/tezacaftor/ivacaftor treatment

BackgroundClinical trials with elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis (PWCF) were associated with significant improvements in percent predicted forced expiratory volume in one second (ppFEV1), sweat chloride, weight and quality of life in the respiratory domain from the cystic fibrosis questionnaire revised (CFQ-R). Limited data exists on its effect on structural lung disease and inflammatory cytokines.MethodsIn a real-world setting with 61 PWCF, we prospectively recorded FEV1, sweat chloride, body mass index (BMI), and CFQ-R at baseline, 3- and 6-months post commencement of ETI. In addition, changes in ultra-low dose computed tomography (ULD-CT) Bhalla score, peripheral-blood and sputum inflammatory-cytokines, and patient-reported outcome measures (PROMs) including sino-nasal outcomes test-22 (SNOT-22), and fatigue scale (FACIT-Fatigue).ResultsSignificant improvements in ppFEV1 (p=0.0001), sweat chloride (p&lt;0.0001), and BMI (p=0.0147) post-ETI treatment were noted. ULD-CT scores demonstrated reductions in peri-bronchial thickening, mucus plugging, and total Bhalla score (p&lt;0.001), and improvements in emphysema extent (p&lt;0.0027). Improvements in systemic inflammatory status were seen with a reduction in interleukin (IL)-1β (p=0.0049), IL-6 and IL-8 (p&lt;0.0001), and increasing IL-10 (p=0.004). Sputum cytokine analysis was not performed as only 4 of 61 patients spontaneously expectorated sputum post ETI. PROMs improved significantly for the SNOT-22 (p&lt;0.0001), FACIT-Fatigue score (p=0.0001), and CFQ-R domains including; respiratory(p&lt;0.0001), physical (p=0.007), vitality (p=0.0004), treatment burden (p=0.0028), health (p=0.0007), social (p=0.0073), weight (p=0.0068), and role/school domain (p=0.0018).ConclusionETI responders, demonstrate significant improvements in CT imaging, circulating cytokines and PROMs which may be of further use evaluating CFTR modulation treatment response.

Usefulness of Mepolizumab for Mucus Plugs.

Usefulness of Mepolizumab for Mucus Plugs.

Biologics and airway remodeling in asthma: early, late, and potential preventive effects.

Although airway remodeling in severe and/or fatal asthma is stil considered irreversible, its individual components as a cause of clinical symptoms and/or lung function changes remain largely unknown. While inhaled glucocorticoids have not consistently been shown to affect airway remodeling, biologics targeting specific pathways of airway inflammation have been shown to improve lung function, mucus plugging, and airway structural changes that can exceed those seen with glucocorticoids. This superiority of biologic treatment, which cannot be solely explained by insufficient doses or limited durations of glucocorticoid therapies, needs to be further explored. For this field of research, we propose a novel classification of the potential effects of biologics on airway remodeling into three temporal effects: early effects (days to weeks, primarily modulating inflammatory processes), late effects (months to years, predominantly affecting structural changes), and potential preventive effects (outcomes of early treatment with biologics). For the identification of potential preventive effects of biologics, we call for studies exploring the impact of early biological treatment on airway remodeling in patients with moderate-to-severe asthma, which should be accompanied by a long-term evaluation of clinical parameters, biomarkers, treatment burden, and socioeconomic implications.

Ivacaftor ameliorates mucus burden, bacterial load, and inflammation in acute but not chronic P. aeruginosa infection in hG551D rats

BackgroundNewly approved highly effective modulation therapies (HEMT) have been life-changing for people with CF. Although these drugs have resulted in significant improvements in lung function and exacerbation rate, bacterial populations in the lung have not been eradicated. The mechanisms behind the continued colonization are not completely clear.MethodsWe used a humanized rat to assess the effects of ivacaftor therapy on infection outcomes. Rats harbor an insert expressing humanized CFTR cDNA, including the G551D mutation. hG551D rats were treated with ivacaftor either during or before infection with P. aeruginosa. The response to infection was assessed by bacterial burden in the lung and mucus burden in the lung.ResultsWe found that hG551D rats treated with ivacaftor had reduced bacteria present in the lung in the acute phase of the infection but were not different than vehicle control in the chronic phase of the infection. Similarly, the percentage of neutrophils in the airways were reduced at the acute, but not chronic, timepoints. Overall weight data indicated that the hG551D rats had significantly better weight recovery during the course of infection when treated with ivacaftor. Potentiation of the G551D mutation with ivacaftor resultant in short-circuit current measurements equal to WT, even during the chronic phase of the infection. Despite the persistent infection, hG551D rats treated with ivacaftor had fewer airways with mucus plugs during the chronic infection.ConclusionsThe data indicate that the hG551D rats have better outcomes during infection when treated with ivacaftor compared to the vehicle group. Rats have increased weight gain, increased CFTR protein function, and decreased mucus accumulation, despite the persistence of infection and inflammation. These data suggest that ivacaftor improves tolerance of infection, rather than eradication, in this rat model.

Liquid plugs in narrow tubes: application to airway occlusion

We study liquid plugs in the pulmonary airways based on the two-phase axisymmetric weighted residual integral boundary-layer model of Dietze et al. (J. Fluid Mech., vol. 894, 2020, A17), which was originally developed to study liquid films coating the inner surface of a cylindrical tube in interaction with a core gas flow. The augmented form of this model, which was never applied beyond a proof of concept, allows for the representation of liquid pseudo-plugs. Here, we demonstrate its predictive power vs experiments and direct numerical simulations, in terms of the dynamics of plug formation and the characteristics of developed liquid plugs, such as their shape, flow field, speed and length, as well as the associated wall stresses and their spatial derivatives. In particular, we show that the augmented model allows us to establish a direct continuation path from travelling-wave solutions (TWS) to travelling-plug solutions (TPS). We then apply the model to predict mucus plugs in the conducting zone of the tracheobronchial tree, based on the lung architecture model of Weibel. We proceed by numerical continuation of travelling-state solutions in terms of the airway generation, whereby we impose the wavelength of the linearly most-amplified convective instability (CI) mode or that of the absolute instability (AI) mode. We identify the critical airway generation for liquid-plug formation (TWS/TPS transition), maximum potential for wall-stress-induced epithelial cell damage and CI/AI transition, and investigate how these phenomena are affected by the main control parameters, i.e. airway orientation vs gravity, air flow rate, mucus properties and airway size.

Is There a Correlation Between the Location of the Clot in the Pulmonary Arterial Tree with the Location of the Mucus Plug in the Pulmonary Bronchial Tree in Patients with chronic obstructive pulmonary disease Experiencing Pulmonary Embolism? Novel Findings.

The study aimed to investigate the impact of mucus plugs on the localization of clots in pulmonary embolisms among chronic obstructive pulmonary disease (COPD) patients. The retrospective study examined 200 participants diagnosed with both COPD and pulmonary embolism. Of these, 100 patients exhibited mucus plugs in the segmental and subsegmental branches of the pulmonary bronchial tree, while the remaining 100 did not, using computed tomography images for diagnosis. Data collection encompassed a comprehensive review of patient records, including medical history and imaging reports, to determine the presence of mucus plugs and the localization of clots in pulmonary embolism cases. Patients with mucus plugs exhibited a notably longer duration of COPD (P = .021) and a higher mean pulmonary arterial occlusion index (23 vs. 12, P = .001). Moreover, the prevalence of clots in major pulmonary arteries was significantly elevated in the mucus plug group compared to the non-mucus plug group (P < .05). Conversely, patients without mucus plugs displayed a higher incidence of clots in segmental and subsegmental arteries (P < .001). Strong positive correlations existed between mucus plugs in segmental branches and clots in major pulmonary arteries, with moderate to strong correlation coefficients (0.51 to 0.62, P < .05). Additionally, strong negative correlations were observed between mucus plugs in segmental branches and clots in segmental and subsegmental arteries, with correlation coefficients (CC) ranging from -0.74 to -0.76 (P < .05). Similarly, a significant negative correlation was noted between mucus plugs in subsegmental branches and clots in subsegmental arteries (CC: -0.68 and -0.71, P < .05). The results suggest that mucus plugs may be associated with increased severity of COPD, higher pulmonary arterial occlusion index, and altered clot distribution within the pulmonary artery tree. These findings emphasize the importance of recognizing mucus plugs as a key consideration in COPD assessment and management, potentially influencing disease severity, vascular remodeling, and thrombotic risk management.

Refractory phenotype of Aspergillus-sensitized asthma with bronchiectasis and allergic bronchopulmonary aspergillosis

BackgroundSensitization to Aspergillus, mucus plugs, and bacterial colonization may coexist and relate to a refractory phenotype during follow-up in asthma with bronchiectasis and allergic bronchopulmonary aspergillosis (ABPA). ObjectiveThis study aimed to clarify the features of Aspergillus-sensitized refractory asthma with bronchiectasis and determine the refractory phenotype in this population and ABPA. MethodsThis study included cases with the oldest available A. fumigatus-specific IgE data and chest computed tomography images from a nationwide survey of refractory asthma with bronchiectasis. The characteristics of the A. fumigatus-IgE positive (Af sIgE+) group were investigated and compared with its nonsensitized counterpart (Af sIgE−) and ABPA group. Cluster analysis was conducted to determine the refractory phenotype. ResultsThe Af sIgE+ group (n = 35) demonstrated type-2 inflammation levels intermediate between the ABPA (n = 42) and Af sIgE− (n = 38) groups while exhibiting higher blood monocyte counts than Af sIgE− group. Cluster analysis conducted in patients with ABPA and Af sIgE+ newly determined two clusters: one was characterized by a younger age of asthma onset with fungal detection in sputum and the other was characterized by mucus plugs, inflammation with eosinophil and monocyte, which was significantly related to mucus plugs, airflow limitation, and trend to show exacerbation. In the latter cluster, mucus plugs persisted and 30% yielded Pseudomonas aeruginosa in the sputum <5 years later. ConclusionThe refractory phenotype with persistent mucus plugs was identified in Aspergillus-sensitized refractory asthma with bronchiectasis and ABPA. Mucus plug prevention is warranted.

Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD.

Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene. Associations between ordinal mucus plug score categories (0/1-2/≥3) and prospectively-ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate-to-severe) and/or ER/hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Among 3,250 participants in COPDGene (mean±SD age 63.7±8.4 years, FEV1 50.6%±17.8% predicted, 45.1% female) and 1,716 participants in ECLIPSE (age 63.3±7.1 years, FEV1 48.3%±15.8% predicted, 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio, aRR [95%CI]=1.07[1.05-1.09] and 1.15[1.1-1.2] in COPDGene; aRR=1.06[1.02-1.09] and 1.12[1.04-1.2] in ECLIPSE, respectively) for prospective moderate-to-severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR=1.05[1.01-1.08] and 1.09[1.02-1.18] in COPDGene; aRR=1.17[1.07-1.27] and 1.37[1.15-1.62] in ECLIPSE, respectively). CT-based mucus plugs are associated with an increased risk for future COPD AEs.

Requirement for Fucosyltransferase 2 in Allergic Airway Hyperreactivity and Mucus Obstruction.

Mucus hypersecretion is an important pathological problem in respiratory diseases. Mucus accumulates in the airways of people with asthma, and it contributes to airflow limitation by forming plugs that occlude airways. Current treatments have minimal effects on mucus or its chief components, the polymeric mucin glycoproteins MUC5AC and MUC5B. This treatment gap reflects a poor molecular understanding of mucins that could be used to determine how they contribute to airway obstruction. Due to the prominence of glycosylation as a defining characteristic of mucins, we investigated characteristics of mucin glycans in asthma and in a mouse model of allergic asthma. Mucin fucosylation was observed in asthma, and in healthy mice it was induced as part of a mucous metaplastic response to allergic inflammation. In allergically inflamed mouse airways, mucin fucosylation was dependent on the enzyme fucosyltransferase 2 (Fut2). Fut2 gene deficient mice were protected from asthma-like airway hyperreactivity and mucus plugging. These findings provide mechanistic and translational links between observations in human asthma and a mouse model that may help improve therapeutic targeting of airway mucus.