Mucus Plugging Research Articles

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

AbstractAlthough 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.

Acute Respiratory Failure Due to Mucous Plug in a Patient With Tropical Spastic Paraparesis

Acute Respiratory Failure Due to Mucous Plug in a Patient With Tropical Spastic Paraparesis

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.

Utility of Flexible Bronchoscopy as an Interventional Tool in Children: A Single-Center Cross-Sectional Study

AbstractThe aim of this study was to study the utility of pediatric flexible bronchoscopy as an interventional tool. This is a prospective study conducted in a tertiary care hospital. The studied patients underwent flexible bronchoscopy for various diagnostic and therapeutic reasons. The endpoint was to document the type of therapeutic procedure done in a patient, success rate, and any procedural complications encountered. During the 7-year period, a total of 824 different bronchoscopic procedures were conducted. The majority of procedures were for diagnostic reasons. A total of 68 therapeutic procedures were performed successfully, which included foreign body retrieval in 46 patients, bronchoscopic intubation in 5 patients, transbronchial needle aspiration (TBNA) in 4 patients, dilatation of tracheal stenosis in 4 patients, mucus plug removal in 3 patients for lung collapse, postoperative hydatid membrane removal in 3 patients, whole lung lavage in 2 patients, and transbronchial needle biopsy (TBNB) for suspected fibrosing mediastinitis in 1 patient. The 7-year audit of therapeutic role of flexible bronchoscopy (FB) in children revealed that the procedure is safe and can be utilized for many therapeutic procedures in children, including removal of aspirated foreign bodies, bronchoscopic intubation, dilatation of tracheal stenosis, treatment of atelectasis, and collection of biopsy specimens from the mediastinum. The procedure is safe and carried no major complication rate.

The Benefits of Silicone Laryngectomy Tubes at the Time of Laryngectomy-A Case Series Spanning 17 Years.

Although total laryngectomy (TL) is a well-established surgical procedure with clear functional or oncologic indications, the peri- and postoperative care for those undergoing TL is variable, particularly regarding postlaryngectomy tracheostoma management. This study examined TL outcomes from a single institution with the immediate perioperative use of soft silicone laryngectomy tubes. More specifically, we explored potential complications associated with immediate perioperative use of a flexible laryngectomy tube (LaryTube and StomaSoft) and the use of heat and moisture exchange (HME) devices in association with peri- and postoperative care. A case series including all patients undergoing TL by one primary surgeon at a tertiary care hospital between 2006 and 2023 were assessed. Variables of interest included hospital average length of stay (LOS) in hospital, use of laryngectomy tube and an HME, primary tracheoesophageal puncture voice restoration at time of TL, discharge feeding, stoma-related complications, and overall complications. Seventy-two patients were included over the study period, and all utilized a laryngectomy tube and HME in the perioperative period without complications. Fifty-six patients (77.7%) had concurrent neck dissections and nine (15%) underwent total laryngopharyngectomy. Sixty-two patients (86%) underwent TL for squamous cell carcinoma of the larynx or hypopharynx and 35 of these (56%) were salvage surgeries. Mean LOS was 8.4 (3-45) days, and 63 patients (88%) were discharged with nasal gastric tube feeding. Of the six patients (8%) who were readmitted for complications, zero (0%) were related to the laryngectomy tube or to stoma-related complications (e.g., dehiscence, infection, mucous plugging). No patient who utilized a laryngectomy tube and HME device in the perioperative period experienced stomal stenosis. Laryngectomy tubes combined with an HME can be employed safely and successfully in a high percentage of laryngectomy patients placed perioperative. No instances of postlaryngectomy tracheostoma stenosis occurred in association with perioperative laryngectomy tube with HME use. These collective data support the use of a laryngectomy tube with HME in the immediate perioperative period, with low risk of complications.

High-Frequency Percussive Ventilation: A Promising Rescue Strategy in Severe Lung Disease of Extremely Low Gestational Age Neonates.

Objective: The aim of this study was to evaluate high-frequency percussive ventilation (HFPV) as a rescue strategy for extremely low gestational age neonates (ELGANs) with severe lung disease. Methods: This is a retrospective review of 16 ELGANs with severe lung disease who were placed on HFPV following a lack of improvement on other modes of conventional and high-frequency ventilation. Results: The gestational age of these 16 infants was 25 (24, 26) weeks and their birth weight was 640 (535, 773) grams [median (IQR)], with the survivors being more immature compared to those who died [24 (23, 26) and 26 (25, 28) weeks, respectively; (p = 0.04)]; and with an overall mortality of 31% (N = 5). Of those who died, 60% were SGA (p = 0.02). Following placement on HFPV, the survivors had a statistically significant decrease in their respiratory severity scores (RSSs) [11 (9, 14) to 6 (5, 13), p = 0.03] compared to those who did not survive [15 (11, 16) to 11 (6.8, 14.5), p = 0.32] due to an improvement in their oxygenation [FiO2: 0.95 (0.85, 1) to 0.6 (0.4, 0.9), p = 0.01; compared to 1 (1, 1) to 1 (0.7, 1); survivors and non-survivors, respectively; p = 0.32]. Chest X-rays also showed significantly improved aeration due to decreased areas of atelectasis in those who survived. Conclusions: HFPV may be an appropriate rescue mode of high-frequency ventilation in the ELGAN population with severe lung disease, particularly for patients with impaired oxygenation and ventilation difficulties due to shifting atelectasis and mucous plugging.

Clinical characteristics and factors associated with mucus plugs under bronchoscopy in children hospitalized for acute asthma attack.

To describe clinical characteristics of hospitalized children with acute asthma attacks complicated with mucus plugs and to investigate the factors associated with mucus plugs in asthma children. This retrospective study analyzed hospitalized children and adolescents with acute asthma attacks from January 2016 to December 2021. The demographic information and characteristics were collected. Subjects were categorized into the mucus plug group and the control group based on the bronchoalveolar lavage results. The Logistic regression analyses were utilized to assess the relative factors associated with mucus plugs. All data were analyzed using SPSS 22.0. This study included 242 individuals. Out of the 151 subjects who underwent bronchoscopy, 62.9% were classified in the mucus plug group and 37.1% in the control group. The subjects with dyspnea had a higher proportion in the mucus plug group (52.6% vs. 26.8%). The serum total IgE level of the mucus plug group was lower than the control group. The proportion of subjects who were diagnosed with asthma for the first time during hospitalization (87.4% vs. 76.8%) and combined with respiratory infection (91.6% vs. 82.1%) in the mucus plug group might be higher than that in the control group. More subjects in the mucus plug group were administered systemic glucocorticoid, magnesium sulfate, aminophylline, and mucolytic drugs after hospitalization. In multivariable analysis, diagnosed with asthma for the first time during hospitalization (OR = 4.404; 1.101-17.614), dyspnea (OR = 4.039; 1.306-12.496), and cesarean (OR = 0.274; 0.092-0.812) might be associated with mucus plug in children hospitalized for an acute asthma attack. While our retrospective study suggests that some clinical features of children hospitalized with asthma who have mucus plugs differ from those without, further studies are required.

Normal Saline Versus Hypertonic Saline for Airway STENT Maintenance: SALTY STENT Study.

Mucus plugging is a common complication of airway stenting. There is no data or guidance on the best airway hygiene regimen and consequently wide practice variation exists. This single-center, nonblinded, randomized, pilot study aims to evaluate the effectiveness and safety of nebulized 3% saline (3%S) versus normal saline (NS) in reducing the incidence of mucus plugging in adult patients that undergo central airway stent placement. Patients were enrolled immediately after stent placement and randomized to nebulized 3%S or NS (3mL) 3 times a day. Patients were scheduled for surveillance bronchoscopy in 4 to 6 weeks. Unscheduled bronchoscopies due to symptomatic mucus plugging were recorded. From December 2022 to March 2024, 37 patients were screened, and 35 were enrolled. Four in the 3%S and 8 in the NS group did not undergo a surveillance bronchoscopy and were excluded from the final analysis. During surveillance bronchoscopy for the 3%S (n=13) and NS (n=10) groups, obstructive mucus plugging was noted in 7.7% versus 40%, granulation requiring intervention in 7.7% versus 10%, and >25% circumferential biofilm in 0% versus 30%, respectively. In the 3%S versus NS groups, 0% versus 20% of patients required an unscheduled bronchoscopy due to mucus plugging. There were no side effects reported with the daily use of 3%S or NS. Nebulized 3%S is safe and may be equally or more effective than NS in preventing obstructive mucus plugging in patients who undergo airway stenting. A larger blinded randomized controlled trial is necessary to confirm this finding.

Tracheal Replacement: A Scoping Review

Abstract Objective To summarize patient characteristics and outcomes for the historical and current methods of long-segment tracheal replacement in humans. Materials and Methods A single reviewer screened the abstracts and full texts using Covidence for file management. Studies published in English that reported human subjects with circumferential or near-circumferential (&gt;270 degrees) cervical tracheal replacements were included. Articles with subjects treated with primary anastomosis alone, retracted articles, abstracts, expert opinion articles, and conference presentations were excluded. Results A total of 32 articles were included in the review reporting 156 cases of long-segment tracheal replacement including synthetic (alive at 1–8 years n = 6/64), regenerative medicine (dead at 15 days–55 months n = 4, not reported n = 6), cadaveric tracheal allograft (alive at 5 months–10 years n = 32/38), aortic allograft (alive at 6–85 months n = 12/16), free tissue transfer (alive at 6–108 months n = 13/21), allotransplantation (alive at 6–24 months n = 5/8), and vascular composite allograft (VCA) (alive at 20 months n = 1/1). Conclusion Silicone and Marlex prostheses have poor long-term outcomes. The cadaveric tracheal allograft can only replace near-circumferential tracheal defects and is therefore limited to benign tracheal pathology. Inadequate structural support plagues the aortic allograft and often requires numerous invasive procedures and maintenance of an intraluminal stent. A lack of mucociliary clearance exists in all methods of tracheal replacement except cadaveric tracheal allograft and VCA and can cause fatal mucous plugging and chronic pulmonary infections. VCA and allotransplantation require long-term immunomodulation therapy.

Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue.

Asthma is characterized by lung eosinophilia, remodeling, and mucus plugging, controlled by adaptive Th2 effector cells secreting IL-4, IL-5, and IL-13. Inhaled house dust mite (HDM) causes the release of barrier epithelial cytokines that activate various innate immune cells like DCs and basophils that can promote Th2 adaptive immunity directly or indirectly. Here, we show that basophils play a crucial role in the development of type 2 immunity and eosinophilic inflammation, mucus production, and bronchial hyperreactivity in response to HDM inhalation in C57Bl/6 mice. Interestingly, conditional depletion of basophils during sensitization did not reduce Th2 priming or asthma inception, whereas depletion during allergen challenge did. During the challenge of sensitized mice, basophil-intrinsic IL-33/ST2 signaling, and not FcεRI engagement, promoted basophil IL-4 production and subsequent Th2 cell recruitment to the lungs via vascular integrin expression. Basophil-intrinsic loss of the ubiquitin modifying molecule Tnfaip3, involved in dampening IL-33 signaling, enhanced key asthma features. Thus, IL-33-activated basophils are gatekeepers that boost allergic airway inflammation by controlling Th2 tissue entry.

The triple radiologic asthma phenotype is associated with worse disease control

BackgroundEfforts have been made to combine radiographical biomarkers such as bronchiectasis or bronchial wall thickness (BWT) to identify asthma sub-phenotypes and their clinical implications. ObjectiveTo assess whether a composite triple radiological phenotype measured by high resolution computed tomography comprising BWT, mucus plug score (MPS) and mediastinal lymph node (MLN) size might provide a better insight into sub-phenotypes in persistent asthma. MethodsOne hundred and twelve patients with moderate-to-severe asthma were included in this retrospective observational study. A binary method was used to classify patients according to median values for: pooled MLN≥3.6mm; BWT as pooled wall area ≥50% of the total airway area; and MPS≥1 where a mucus plug was considered positive if complete bronchial obstruction was imaged more than 2 cm from a pleural surface. ResultsPatients with the triple imaging phenotype exhibited significantly worse asthma control questionnaire scores exceeding minimal clinical important difference, a higher prevalence of concomitant chronic rhinosinusitis with nasal polyposis and a greater total IgE level. ConclusionWe have demonstrated an association between poorer symptom control and the triple radiological asthma phenotype.

Impact of Nebulized BromAc® on Mucus Plug Clearance in a Mechanically Ventilated Ex Vivo Ovine Lung Model of Obstructive Respiratory Conditions.

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.

Update on the Role of Chest Imaging in Cystic Fibrosis.

Cystic fibrosis is a genetic disease with multisystem involvement and associated morbidity and mortality that are most directly related to progressive lung disease. The hallmark findings of cystic fibrosis in the lungs are chronic inflammation and infection, leading to progressive loss of pulmonary function and often requiring lung transplant. Predominant lung findings include mucous plugging, bronchiectasis, and air trapping, often with associated atelectasis, consolidation, and emphysema; these findings form the basis of several clinical scoring systems that are used for imaging assessment. Recently, there have been major breakthroughs in the pharmacologic management of cystic fibrosis, including highly effective modulator therapies that directly target the underlying cystic fibrosis transmembrane conductance regulator molecular defect, often leading to remarkable improvements in lung function and quality of life with corresponding significant improvements in imaging markers. The authors review current guidelines regarding cystic fibrosis with respect to disease monitoring, identifying complications, and managing advanced lung disease. In addition, they discuss the evolving role of imaging, including current trends, emerging technologies, and proposed updates to imaging guidelines endorsed by international expert committees on cystic fibrosis, which favor increased use of cross-sectional imaging to enable earlier detection of structural changes in early disease and more sensitive detection of acute changes in advanced disease. It is important for radiologists to be familiar with these trends and updates so that they can most effectively assist clinicians in guiding the management of patients with cystic fibrosis in all stages of disease. ©RSNA, 2024.

The effect of prior hysterosalpingo-foam sonography or hysterosalpingography on tubal patency: a secondary analysis of a randomized controlled trial.

Does hysterosalpingo-foam sonography (HyFoSy) prior to hysterosalpingography (HSG) or HSG prior to HyFoSy affect visible tubal patency when compared HSG or HyFoSy alone? Undergoing either HyFoSy or HSG prior to tubal patency testing by the alternative method does not demonstrate a significant difference in visible tubal patency when compared to HyFoSy or HSG alone. HyFoSy and HSG are two commonly used visual tubal patency tests with a high and comparable diagnostic accuracy for evaluating tubal patency. These tests may also improve fertility, although the underlying mechanism is still not fully understood. One of the hypotheses points to a dislodgment of mucus plugs that may have disrupted the patency of the Fallopian tubes. This is a secondary analysis of the randomized controlled FOAM study, in which women underwent tubal patency testing by HyFoSy and HSG, randomized for order of the procedure. Participants either had HyFoSy first and then HSG, or vice versa. Here, we evaluate the relative effectiveness of tubal patency testing by HyFoSy or HSG prior to the alternative tubal patency testing method on visible tubal patency, compared to each method alone. Infertile women aged between 18 and 41 years scheduled for tubal patency testing were eligible for participating in the FOAM study. Women with anovulatory cycles, endometriosis, or with a partner with male infertility were excluded. To evaluate the effect HyFoSy on tubal patency, we relied on HSG results by comparing the proportion of women with bilateral tubal patency visible on HSG in those who underwent and who did not undergo HyFoSy prior to their HSG (HyFoSy prior to HSG versus HSG alone). To evaluate the effect of HSG on tubal patency, we relied on HyFoSy results by comparing the proportion of women with bilateral tubal patency visible on HyFoSy in those who underwent and who did not undergo HSG prior to their HyFoSy (HSG prior to HyFoSy versus HyFoSy alone). Between May 2015 and January 2019, we randomized 1160 women (576 underwent HyFoSy first followed by HSG, and 584 underwent HSG first followed by HyFoSy). Among the women randomized to HyFoSy prior to HSG, bilateral tubal patency was visible on HSG in 467/537 (87%) women, compared with 472/544 (87%) women who underwent HSG alone (risk difference 0.2%; 95% CI: -3.8% to 4.2%). Among the women randomized to HSG prior to HyFoSy, bilateral tubal patency was visible on HyFoSy in 394/471 (84%) women, compared with 428/486 (88%) women who underwent HyFoSy alone (risk difference -4.4%; 95% CI: -8.8% to 0.0%). The results of this secondary analysis should be interpreted as exploratory and cannot be regarded as definitive evidence. Furthermore, it has to be noted that pregnancy outcomes were not considered in this analysis. Tubal patency testing by either HyFoSy or HSG, prior to the alternative tubal patency testing method does not significantly affect visible tubal patency, when compared to alternative method alone. This suggests that both methods may have comparable abilities to dislodge mucus plugs in the Fallopian tubes. The FOAM study was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, or interpretation of the data. H.R.V. reports consultancy fees from Ferring. M.v.W. received a travel grant from Oxford University Press in the role of Deputy Editor for Human Reproduction and participates in a Data Safety and Monitoring Board as an independent methodologist in obstetrics studies in which she has no other role. M.v.W. is coordinating editor of Cochrane Fertility and Gynaecology. B.W.J.M. received an investigator grant from NHMRC (GNT1176437) and research funding from Merck KGaA. B.W.J.M. reports consultancy for Organon and Merck KGaA, and travel support from Merck KGaA. B.W.J.M. reports holding stocks of ObsEva. V.M. received research grants from Guerbet, Merck and Ferring and travel and speaker fees from Guerbet. The other authors do not report conflicts of interest. International Clinical Trials Registry Platform No. NTR4746.

Middle Lobe Syndrome in Children: Three Case Reports and a Brief Review

Background: Middle Lobe Syndrome (MLS) is a pediatric respiratory condition characterized by the collapse of the middle lobe of the right lung or the lingula of the left lung. Historically linked with tuberculosis, contemporary cases primarily involve asthma and other causes, like foreign body aspiration or mucous plug. Case Presentation: We have, herein, analyzed the clinical features and management of three cases of MLS from a single pediatric center. Additionally, we have reviewed 75 articles on pediatric MLS by using common databases, such as PubMed and Medline. Discussion: MLS often poses a diagnostic challenge, presenting with symptoms, like cough, wheezing, and localized rales. Radiological exams, especially chest X-rays and flexible bronchoscopy, are needed for confirming the diagnosis, particulary in challenging cases. Both obstructive and non-obstructive factors contribute to MLS. Conclusion: A comprehensive understanding of MLS, its diverse causes, and the significance of early diagnosis is crucial for effective management. Treatment should target the underlying cause. Prompt intervention may offer a positive outcome and help prevent complications, like bronchiectasis.