Search Results (27)

Background: Airway mucus plugging is a key but long-overlooked mechanism of persistent airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Type 2 (T2) cytokines, particularly interleukin (IL)-4 and IL-13, drive goblet cell metaplasia, MUC5AC overexpression, and impaired mucociliary clearance, while eosinophil-derived products increase mucus viscosity and promote plug persistence. Methods: A comprehensive narrative review was conducted by searching PubMed and ClinicalTrials.gov databases from inception to February 2026. Search terms included “mucus plugs,” “mucus plugging,” “biologics,” “dupilumab,” “tezepelumab,” “mepolizumab,” “benralizumab,” “IL-4,” “IL-13,” “MUC5AC,” “quantitative CT,” “functional respiratory imaging,” “asthma,” and “COPD.” Studies were included if they reported original data or systematic evidence on mucus plug quantification, biologic-mediated changes in mucus plug scores, or imaging modalities for mucus assessment in asthma or COPD. Editorials, case reports with fewer than three patients, and studies not available in English were excluded. Two authors (P.-V.M. and A.C.) independently screened titles and abstracts; discrepancies were resolved by consensus. Randomized controlled trials, observational studies, and preclinical studies evaluating mucus plug outcomes and T2-targeted therapies were included. Reference lists of retrieved articles were hand-searched for additional relevant publications. Results: A recent systematic review identified multiple randomized controlled trials and observational studies that showed CT-assessed mucus plug scores go down with biologic therapies targeting the T2 pathway in asthma. Observational data extend this evidence to anti-IL-5/IL-5Rα agents. The VESTIGE trial provided the first functional respiratory imaging evidence of mucus plug resolution with dupilumab. In COPD, the BOREAS/NOTUS and MATINEE trials established the efficacy of dupilumab and mepolizumab in eosinophilic phenotypes; however, differences in inclusion criteria—particularly regarding FeNO thresholds and prior exacerbation burden—may explain divergent effects on lung function endpoints. Mucus plug outcomes have not been evaluated in COPD biologic trials. Quantitative imaging modalities, including HRCT mucus plug scoring, functional respiratory imaging, and hyperpolarized gas MRI, now enable objective assessment of mucus burden. Conclusions: Mucus plugging meets the definition of a treatable trait: it can be measured with CT scoring, it matters clinically, and it responds to T2 cytokine blockade. Adding mucus plug assessment to routine clinical evaluation, together with mucolytic strategies where needed, could move treatment decisions from empirical to biology-based across the asthma–COPD spectrum. Further studies are needed to confirm that mucus plug scoring works as a biomarker of treatment response in COPD and to test whether combining biologics with mucolytics improves outcomes. Full article

Context/Objectives: In patients with COPD (chronic obstructive pulmonary disease), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection represents an overlap of viral injury on a lung already affected by pathological mucus, altered mucociliary clearance, chronic inflammation, and impaired antiviral immunity. Methods: A focused narrative review (2020–2025) was conducted using clinical, experimental, and consensus evidence. The evidence was synthesized qualitatively, with priority given to cohort studies, meta-analyses, and mechanism-focused studies with clinical relevance. Results: Mucus obstruction (“mucus plugs”) is frequent in COPD (41–67%) and is associated with unfavorable outcomes. COPD also increases the risk of post-COVID respiratory sequelae. Bacterial coinfection at presentation is uncommon (3–5%), whereas secondary bacterial infections are more frequent (14–18%), especially in severe disease requiring intensive care, where VA-LRTI/VAP (ventilator-associated lower respiratory tract infection/ventilator-associated pneumonia) become predominant. Sepsis, whether viral or mixed, reflects disease severity and may contribute to functional decline and susceptibility to reinfections; however, the concept of a post-acute “sepsis legacy” in COPD after COVID-19 should currently be regarded as a clinically plausible but still emerging hypothesis rather than an established COPD-specific outcome. During recovery, acute exacerbation risk rises to 5.6% versus 3.9%, peaking in the first 30 days after severe disease (aHR ≈ 8.14). Persistent dyspnea and reduced DLCO (diffusing capacity for carbon monoxide) suggest ARDS-related injury, tissue remodeling, and microvascular dysfunction. Conclusions: In COPD, post-COVID respiratory sequelae result from the interaction of mucus, immunity, and infectious/sepsis-related complications. The first post-discharge month is a critical period requiring careful risk stratification and targeted follow-up. Full article

Mucus plugs are airway-obstructing accumulations of inspissated secretions frequently observed in obstructive lung diseases (OLDs), including chronic obstructive pulmonary disease (COPD), severe asthma, and cystic fibrosis. Their presence on chest CT is strongly associated with airflow limitation, reduced lung function, and increased mortality, making them emerging imaging biomarkers of disease burden and treatment response. However, manual delineation of mucus plugs is labor-intensive, subjective, and impractical for large cohorts, leading most prior studies to rely on coarse segment-level scoring systems that overlook lesion-level characteristics such as size, extent, and location. Automated plug-level quantification remains challenging due to substantial heterogeneity in plug morphology, overlap in attenuation with adjacent vessels and airway walls on non-contrast CT, and pronounced size imbalance in clinical datasets, which are typically dominated by small distal plugs. To address these challenges, we developed and validated a simulation-driven, annotation-free deep learning framework for automated detection and segmentation of airway mucus plugs on non-contrast chest CT. A total of 200 COPD CT scans were analyzed (98 plug-positive, 83 plug-negative, and 19 uncertain). Synthetic mucus plugs were generated within segmented airways by transferring voxel-intensity statistics from adjacent intrapulmonary vessels, preserving realistic morphology and texture while enabling controlled sampling of plug phenotypes. An nnU-Net trained exclusively on synthetic data (S-Model) was evaluated on an independent, expert-annotated test set and compared with an nnU-Net trained on manual annotations using 10-fold cross-validation (M-Model). The S-Model achieved significantly higher detection performance than the M-Model (sensitivity 0.837 [95% CI: 0.818–0.854] vs. 0.757 [95% CI: 0.737–0.776]; 1.91 false positives per scan vs. 3.68; p < 0.001), with performance gains most pronounced for medium-to-large plugs (≥6 mm). This simulation-driven approach enables accurate, scalable quantification of mucus plugs without voxel-wise manual annotation in thin-slice (<1.5 mm) non-contrast chest CT scans. While the framework could, in principle, be extended to other annotation-limited medical imaging tasks, its generalizability beyond this COPD cohort and imaging protocol has not yet been established, and future work is required to validate performance across diverse populations and scanning conditions. Full article

Objectives: To evaluate the loss of quality of life (QoL) in patients with chronic obstructive sialadenitis (COS) using the Chronic Obstructive Sialadenitis Questionnaire (COSQ). Methods: The COSQ was administered to patients diagnosed with COS, with the diagnosis confirmed by sialendoscopy. Epidemiological data, obstructive causes and potentially obstructive entities were collected. QoL was assessed using the COSQ. Results: A total of 344 glands in 278 patients with COS were analyzed. Most patients were women (71.94%), and the main obstructive cause was stenosis (47.96%), followed by lithiasis, lack of papilla distensibility (LPD), and mucus plug. Stenosis was significantly more frequent in the parotid gland and in women, whereas lithiasis predominated in the submandibular gland and in men. The mean COSQ score was 30.55 and it was significantly higher in women (p < 0.005), parotid gland (p < 0.005), and in long-standing cases (p < 0.05). Stenosis and LPD were the obstructive causes with the greatest impact on QoL (p < 0.005), while lithiasis had the least impact. Potentially Obstructive Entities (POEs), such as eosinophilic sialodochitis, Sjögren’s syndrome, or radioiodine-induced sialadenitis, were associated with a notable loss of QoL. Likewise, patients without associated POEs presented significantly lower COSQ values (p < 0.05). Conclusions: COS significantly affects QoL, particularly in women and in cases of parotid gland, stenosis, and LPD. Lithiasis has the least impact on QoL. It is important to standardize a thorough evaluation of COS using validated tools such as the COSQ, which are fundamental for understanding the disease and predicting the outcomes of therapeutic interventions. Full article

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 (T2) asthma endotype. Emerging biomarkers, or older biomarkers with emerging utility, include sputum inflammatory cells (eosinophils, neutrophils, interleukins), thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, eosinophil peroxidase (EPX), Clara/club cell secretory protein (CC16), and quantitative computerized tomography (QCT) imaging biomarkers (evaluating mucus plugging, air trapping, airway wall thickness, small airway remolding) and are increasingly used in clinical trials as secondary endpoints in evaluating efficacy, as well as in the clinical setting at specialized centers. The rapid advances in asthma research, due in part to biomarkers and biologic therapies, may soon standardize an end goal: symptom-free asthma remission without exacerbations. Full article

Elexacaftor–tezacaftor–ivacaftor (ETI) has shown clinical and spirometric benefits in cystic fibrosis (CF). CT remains a vital tool for diagnosing and monitoring structural lung disease. This study aimed to assess the evolution of lung disease, as evaluated through CT, in adults with CF after at least one year of ETI treatment. This ambispective observational analysis assessed lung CT scans performed before initiating ETI and after at least one year of treatment, using the modified Bhalla scoring system. For those patients with an earlier CT scan, a pre-treatment phase analysis was performed. Epidemiological, clinical, and functional parameters were evaluated. Results: Sixty-two patients were included (35 males, median age 30.4 ± 7.87 years). After at least one year of ETI, significant improvements were observed in the global CT Bhalla score (12.2 ± 2.8 vs. 14.0 ± 2.8), peribronchial thickening (1.4 ± 0.6 vs. 1.0 ± 0.4), and mucus plugging (1.6 ± 0.7 vs. 0.8 ± 0.6) (p < 0.001). Spirometry parameters increased significantly: the percentage of the predicted forced expiratory volume in the first second (ppFEV₁) increased from 66.5 ± 19.8 to 77.0 ± 20.4 (p = 0.005) and forced vital capacity (ppFVC) from 80.6 ± 16.4 to 91.6 ± 14.1 (p < 0.001). Additionally, body mass index showed a significant increase. A moderate correlation was found between the Bhalla score and spirometry results. In the pre-treatment phase (n = 52), mucus plugging demonstrated a significant worsening, whereas global CT score, other subscores, and spirometry did not change significantly. Conclusions: In adults with CF, after at least one year of ETI, a significant improvement in structural lung disease was achieved, as reflected by the CT Bhalla score. Full article

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. Full article

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. It can cause blockage of the airways, leading to breathlessness and lung failure. Here, we used a ventilatory setup to demonstrate the effect of BromAc^® in dissolving mucus plugs in a novel ex vivo ovine obstructive lung model. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc^®, and saline control were administered via an Aerogen^® vibrating nebulizer and ventilated for 30 or 60 min. Ventilatory recording of resistance, compliance, and tidal volume was conducted, and rheology pre- and post-treatment were measured. A significant decline in airway resistance (p < 0.0001) compared to the saline control was observed when treated with Bromelain, Ac, and BromAc^®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter time points (p < 0.05) at lower doses of the drugs. Changes in compliance, peak pressure, and tidal volume were not observed after administration of the drugs. Rheology measurements revealed that BromAc^®TM significantly reduced the viscosity of the mucin at the end of 30 min and 60 min time points (p < 0.001) compared to the saline control. BromAc^® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex vivo ovine model. Full article

Bronchial asthma is characterized by airway inflammation, airway hyperresponsiveness, and reversible airway obstruction. Eosinophils contribute to the pathogenesis of airway disease mainly by releasing eosinophil-specific granules, lipid mediators, superoxide anions, and their DNA. Type-2 cytokines such as interleukin (IL)-4 and IL-13 also play roles in the development of bronchial asthma. Among these cytokines, IL-4 is involved in T-cell differentiation, B-cell activation, B-cell differentiation into plasma cells, and the production of immunoglobulin E. Although IL-13 has similar effects to IL-4, IL-13 mainly affects structural cells, such as epithelial cells, smooth muscle cells, and fibroblasts. IL-13 induces the differentiation of goblet cells that produce mucus and induces the airway remodeling, including smooth muscle hypertrophy. IL-4 and IL-13 do not directly activate the effector functions of eosinophils; however, they can induce eosinophilic airway inflammation by upregulating the expression of vascular cell adhesion molecule-1 (for adhesion) and CC chemokine receptor 3 ligands (for migration). Dupilumab, a human anti-IL-4 receptor α monoclonal antibody that inhibits IL-4 and IL-13 signaling, decreases asthma exacerbations and mucus plugs and increases lung function in moderate to severe asthma. In addition, dupilumab is effective for chronic rhinosinusitis with nasal polyps and for atopic dermatitis, and IL-4/IL-13 blocking is expected to suppress allergen sensitization, including transcutaneous sensitization and atopic march. Full article

Background: Primary ciliary dyskinesia (PCD, MIM 244400) is an inherited ciliopathy disorder characterized by recurrent sinopulmonary infections, subfertility, and laterality defects. The true incidence of PCD in Saudi Arabia is not known, but it is likely underdiagnosed due to the high prevalence of consanguineous marriages. In this study, we aim to study the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia to provide guidance to clinicians and researchers studying PCD. Methods: This was a cross-sectional study conducted between 2019 and 2023 in Abha Maternity and Children’s Hospital. Twenty-eight patients with clinically diagnosed PCD were recruited. The diagnosis of PCD was confirmed via whole-exome sequencing. Results: A total of 28 patients from 20 families were identified and recruited for this study. The median age of patients was 7.5 years (IQR = 3, 13 years). The people of different sexes were evenly distributed, and 18 patients (64%) had neonatal respiratory distress (NRD). The median age of diagnosis was 5.5 years (IQR = 2, 11 years), while the age when the first symptoms appeared was 3 months old (IQR = 1, 6 months). The prevalence of a chronic wet cough, chronic rhinosinusitis, ear infections were 100% (n = 28), 78.6% (n = 22), and 67.9% (19), respectively. The most common gene in our study was DNAH5, which represented 17.9% (five out of twenty-eight) of the cases. Furthermore, the remaining pathogenic variants included: 14.3% with RSPH9 in four individuals (three families), 14.3% with DNAI2 in four individuals (two families), and 10.7% with LRRC56 in three individuals (one family). The most common findings on the chest CT scans were consolidation (seen in all patients), mucus plugging (seen in 95%), and bronchiectasis (seen in 77%). In the patients with bronchiectasis, the most commonly affected lobes were the right lower lobe (88%) and left lower lobe (76%). The patients with PCD and situs inversus were more likely to experience NRD than the patients with PCD and situs solitus. The median PICADAR score in the patients with PCD and situs inversus (median: 11.5; Q1: 10–Q3: 12.5) was significantly higher compared to those with PCD and situs solitus (median: 7.5; Q1: 5.8–Q3: 8) (U = 10.5; p < 0.001). Conclusion: This study provides preliminary data on the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia. We found that DNAH5 and RSPH9 genes were the most common genes among the studied population. Furthermore, PCD should be considered for each child with early NRD and laterality defects, and further confirmatory tests are recommended. These findings also highlight the need for greater awareness of the disease in daily clinical practice to facilitate early diagnosis and avoid irreversible lung damage. Full article

Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus. Full article

The availability of highly effective CFTR modulators is revolutionizing the treatment of cystic fibrosis (CF) and drastically improving outcomes. MRI-based imaging modalities are now emerging as highly sensitive endpoints, particularly in the setting of mild lung disease. Adult CF patients were recruited from a single center prior to starting treatment with E/T/I. The following studies were obtained before and after one month on treatment: spirometry, multiple breath nitrogen washout (MBW), ¹H UTE MRI (structural images) and ¹⁹F MRI (ventilation images). Changes between visits were calculated, as were correlations between FEV₁, lung clearance index (LCI), MRI structural scores, and MRI-based ventilation descriptors. Eight subjects had complete datasets for evaluation. Consistent with prior clinical trials, FEV₁ and LCI improved after 28 days of E/T/I use. ¹H UTE MRI detected improvements in bronchiectasis/airway wall thickening score and mucus plugging score after 28 days of therapy. ¹⁹F MRI demonstrated improvements in fractional lung volume with slow gas washout time (FLV↑tau2) and ventilation defect percentage (VDP). Improvements in FLV↑tau2 and VDP correlated with improvement in FEV₁ (r = 0.81 and 0.86, respectively, p < 0.05). This observational study establishes the ability of ¹⁹F MRI and ¹H UTE MRI to detect improvements in lung structure and function after E/T/I treatment. This study supports further development of ¹⁹F MRI and ¹H UTE MRI as outcome measures for cystic fibrosis research and drug development. Full article

This is a prospective, observational study involving three Cystic Fibrosis (CF) adult patients, evaluating the changes in chest magnetic resonance imaging (MRI) three months after the start of elexacaftor/tezacaftor and ivacaftor therapy. MRI showed a drastic reduction in mucus plugging and bronchial wall thickening, with an improvement in the diffusion-weighted MRI score. Similarly, a marked improvement in spirometric parameters, nutritional status, and sweat chloride was observed. Our preliminary data confirm that chest MRI could be a useful tool to assess disease progression in CF patients on modulatory drug therapy. Full article

Ecological networking and in vitro studies predict that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes. The metabolic byproducts from these bacteria facilitate the colonization and growth of CF pathogens like Pseudomonas aeruginosa. Here, a multi-omics study informed the control of putative anaerobic keystone species during a transition in antibiotic therapy of a CF patient. A quantitative metagenomics approach combining sequence data with epifluorescence microscopy showed that during periods of rapid lung function loss, the patient’s lung microbiome was dominated by the anaerobic, mucus-degrading bacteria belonging to Streptococcus, Veillonella, and Prevotella genera. Untargeted metabolomics and community cultures identified high rates of fermentation in these sputa, with the accumulation of lactic acid, citric acid, and acetic acid. P. aeruginosa utilized these fermentation products for growth, as indicated by quantitative transcriptomics data. Transcription levels of P. aeruginosa genes for the utilization of fermentation products were proportional to the abundance of anaerobic bacteria. Clindamycin therapy targeting Gram-positive anaerobes rapidly suppressed anaerobic bacteria and the accumulation of fermentation products. Clindamycin also lowered the abundance and transcription of P. aeruginosa, even though this patient’s strain was resistant to this antibiotic. The treatment stabilized the patient’s lung function and improved respiratory health for two months, lengthening by a factor of four the between-hospitalization time for this patient. Killing anaerobes indirectly limited the growth of P. aeruginosa by disrupting the cross-feeding of fermentation products. This case study supports the hypothesis that facultative anaerobes operated as keystone species in this CF microbiome. Personalized multi-omics may become a viable approach for routine clinical diagnostics in the future, providing critical information to inform treatment decisions. Full article

Aspergillus is increasingly associated with lung inflammation and mucus plugging in early cystic fibrosis (CF) disease during which conidia burden is low and strains appear to be highly diverse. It is unknown whether clinical Aspergillus strains vary in their capacity to induce epithelial inflammation and mucus production. We tested the hypothesis that individual colonising strains of Aspergillus fumigatus would induce different responses. Ten paediatric CF Aspergillus isolates were compared along with two systemically invasive clinical isolates and an ATCC reference strain. Isolates were first characterised by ITS gene sequencing and screened for antifungal susceptibility. Three clusters (A−C) of Aspergillus isolates were identified by ITS. Antifungal susceptibility was variable, particularly for itraconazole. Submerged CF and non-CF monolayers as well as differentiated primary airway epithelial cell cultures were incubated with conidia for 24 h to allow germination. None of the clinical isolates were found to significantly differ from one another in either IL-6 or IL-8 release or gene expression of secretory mucins. Clinical Aspergillus isolates appear to be largely homogenous in their mucostimulatory and immunostimulatory capacities and, therefore, only the antifungal resistance characteristics are likely to be clinically important. Full article