Velopharyngeal Insufficiency Following Furlow Versus Straight Line Repair With Intravelar Veloplasty: A Single-institution Experience.

BACKGROUND: Measurements of postoperative velopharyngeal dysfunction (VPD) can be used to determine the efficacy of a palatoplasty operation. Hypernasality and audible nasal air emission are typical manifestations of VPD during speech. We aimed to longitudinally compare VPD outcomes in postpalatoplasty patients who underwent Furlow repair versus straight line repair with intravelar veloplasty (IVVP). Additionally, we examined the relationship between VPD outcomes and select pre-existing patient characteristics. METHODS: Retrospective chart review was performed to identify primary palatoplasty patients treated from April 2012 to March 2021. Variables collected included gender, syndromic status, primary language, Veau cleft type, type of speech assessment, age at time of surgery, degree of hypernasality, presence of audible nasal air emission, and overall adequacy of velopharyngeal function. Pearson χ2 test and multivariable t tests were used to analyze variables. Logistic regression was used to control for statistically significant variables. RESULTS: Of the 118 patients included, 38 received a Furlow procedure and 80 received a straight line with IVVP procedure. Audible nasal air emission was present in 57.3% of straight line with IVVP patients and 42.9% of Furlow patients, with no statistically significant difference between groups. Clinically significant hypernasality was present in 42.1% of straight line with IVVP patients and 22.9% of Furlow patients (P=0.05). Velopharyngeal function was classified as adequate in 63.5% of straight line with IVVP patients and 83.3% of Furlow patients (P=0.03). However, after stratifying by syndromic versus nonsyndromic status, there was no statistically significant difference between straight line with IVVP and Furlow patients for postoperative hypernasality and velopharyngeal function. CONCLUSIONS: This study suggests that there are no statistically significant differences between straight line with IVVP and Furlow palatoplasty techniques regarding speech outcomes including hypernasality, audible nasal air emission, and overall VP function. Furthermore, select patient characteristics such as gender, primary language, syndromic status, age at repair, and Veau cleft type do not significantly impact postoperative speech outcomes.

Reference Values for the Six Minute Walk Test in Children with Juvenile Idiopathic Arthritis.

AIMS: To (1) describe six-minute walk test (6MWT) reference values for children with Juvenile Idiopathic Arthritis (JIA) and (2) explore predictors of 6MWT distance. A secondary objective was to determine how 6MWT distances of children with JIA compare to those of children without JIA reported in the literature. METHODS: Demographic, clinical, height, weight and 6MWT data were extracted from clinical records of 120 children with JIA (70.8% female, mean age=12.4 ± 3.2 years) who attended a follow-up rheumatology clinic. A total of 272 6MWTs were included in the analyses. Linear mixed effects modeling was used to determine the relationship between predictive variables and 6MWT distance. 6MWT distances were compared to predicted values using published equations for estimating 6MWT distances in children without JIA. RESULTS: Height, weight, and age were predictive of 6MWT distance (R2 = 0.62). Mean 6MWT distances for children with JIA were lower than those reported for children without JIA (p < 0.001). Mean 6MWT distance was 84% and 78% of predicted values for children without JIA. CONCLUSION: The reference values and associated predictive model have application for assessing exercise capacity in children with JIA.

Family satisfaction with telemedicine follow-up after pediatric plastic surgery.

OBJECTIVE: One issue faced at institutions that serve a vast area is patients' ability to travel for perioperative care. Telemedicine is an innovative way of providing care while removing the inconvenience of travel or the hindrance of cost associated with travel. We initiated telemedicine as an option for certain postoperative encounters and assessed patient family satisfaction with this novel approach. METHODS: Our practice offers telemedicine visits to patients who have had simple surgical procedures, identified by a fixed list of CPT codes. Visits are scheduled 7 to 14 days after surgery. Families completed a satisfaction survey after their encounter. RESULTS: A pilot program was initiated from January 2019 to March 2020 using this method of postoperative follow-up. The initial response from families (N = 60) was extremely positive. CONCLUSION: We anticipate the option for telemedicine visits will make postoperative follow-ups more amendable to families, increase adherence rates, and increase access to care.

Cleft Care Packages and the Impact on Postoperative Care Following a Primary Cleft Lip Repair.

OBJECTIVE: To provide caregivers with all the resources needed to care for a surgical site following a primary cleft lip repair and evaluate its efficacy on postoperative care. SETTING/PARTICIPANTS: Caregivers of infants ages 3 to 6 months with a cleft lip and/or palate undergoing a primary repair at the Texas Children's Hospital. METHODS: Packages were given to caregivers at discharge following repair. Packages included instructions and supplies needed for surgical site care. At discharge an advanced practice provider obtained informed consent and a questionnaire that established baseline knowledge of surgical site care. Following the questionnaire, the advanced practice provider demonstrated how to care for the site using the package provided. Assessment of scar healing, nasal stent compliance, and ease of care was evaluated at postoperative follow up. RESULTS: Thirty-two families were enrolled in this study. Our data supports that caregivers who are provided resources to care for the site had increased comfort level, preparedness, and compliance rates following a primary cleft lip repair. Eighty-four percent of respondents strongly agreed that the package provided aided in preparedness for site care with 100% of respondents recommending the resources to future families undergoing a cleft lip repair. CONCLUSIONS: Caregivers feel comfortable and equipped with their ability to care for their child's repaired cleft lip when given the appropriate instructions and supplies. In addition, they would recommend the packages to future families following a repair. Empowering families to be proactive in postoperative care will potentially lead to better outcomes in cleft care.

Muc5b is required for airway defence.

Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

Orthognathic Surgical Treatment in a Patient With Hyperimmunoglobulin E Syndrome.

Autosomal-dominant hyperimmunoglobulin E syndrome (HIES), or Job syndrome, is a rare, multisystem, primary immunodeficiency disorder. Additionally, patients may also suffer from connective tissue, dental, and bone malformations. While current management of HIES is directed at prophylactic antibiotics to prevent infections, there is limited work describing surgical considerations for these patients, particularly with respect to hardware placement. Here we report a case of a patient with HIES who underwent orthognathic surgery for maxillary advancement and mandibular setback to address his severe class III malocclusion. The patient's postoperative course was complicated by significant infection, requiring multiple operations and ultimately, hardware removal after bone healing. Although this patient ultimately had a good outcome, the role of orthognathic surgery with implant placement in patients with HIES should be approached with caution and careful consideration.

A common MUC5B promoter polymorphism and pulmonary fibrosis.

BACKGROUND: The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk. METHODS: Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 3.4-Mb region of chromosome 11p15 in 82 families. We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls. MUC5B expression was assessed in lung tissue. RESULTS: Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes. The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P=1.2×10(-15); allelic association with idiopathic pulmonary fibrosis, P=2.5×10(-37)). The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 6.8 (95% confidence interval [CI], 3.9 to 12.0) and 20.8 (95% CI, 3.8 to 113.7), respectively, for familial interstitial pneumonia and 9.0 (95% CI, 6.2 to 13.1) and 21.8 (95% CI, 5.1 to 93.5), respectively, for idiopathic pulmonary fibrosis. MUC5B expression in the lung was 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0.001). The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 37.4 times as high as in unaffected subjects homozygous for the wild-type allele, P<0.001). MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis. CONCLUSIONS: A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis. Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis. (Funded by the National Heart, Lung, and Blood Institute and others.).

Plastic surgeon closure is comparable to orthopedic closure when a perioperative optimization protocol is instituted for pediatric patients with neuromuscular scoliosis.

BACKGROUND CONTEXT: Since 2015, plastic multilayer closure (PMC) has been gaining attraction due to improved wound healing outcomes for medically complex patients. Plastic multilayer closure has been readily used for complex spine surgery closures in patients susceptible to wound healing issues (ie, dehiscence, surgical site infection [SSI]). However, PMC requires extensive soft tissue manipulation compared with standard orthopedic spine surgeon closure (SOC) and can result in extended operative times, increased transfusion rates, and more frequent returns to the operating room. PURPOSE: From 2016 to 2019, our institution implemented a perioperative protocol designed to decrease postoperative complication rates in NMS patients. A retrospective cohort study was performed to determine if PMC imparted advantages over SOC above and beyond that from the perioperative protocol. STUDY DESIGN/SETTING: Retrospective study at a single academic institution. PATIENT SAMPLE: Eighty-one pediatric patients with neuromuscular scoliosis undergoing spinal fixation surgery. OUTCOME MEASURES: Postoperative wound complications such as surgical site infection, hematoma, and superficial/deep dehiscence were the main outcome measures. Respiratory and neuromuscular complications along with duration of surgery were also recorded. METHODS: A retrospective review was conducted of NMS patients undergoing spinal fixation at a single academic pediatric hospital over 4 years. Cases were labeled as SOC (n=41) or PMC (n=40) based on the closure technique applied. Reported 90-day complications were evaluated as the primary outcome. RESULTS: Of the 81 reviewed patients, 45 reported complications, roughly equal between the study groups. While we found no statistically significant differences in rates of postoperative complications or SSIs, SOC cases were 30 minutes shorter on average with fewer returns to the operating room for additional surgery. CONCLUSIONS: With the implementation of our perioperative protocol for NMS patients, PMC did not result in fewer complications than SOC but the surgeries did take longer.

Predicting the location of human perirhinal cortex, Brodmann's area 35, from MRI.

The perirhinal cortex (Brodmann's area 35) is a multimodal area that is important for normal memory function. Specifically, perirhinal cortex is involved in the detection of novel objects and manifests neurofibrillary tangles in Alzheimer's disease very early in disease progression. We scanned ex vivo brain hemispheres at standard resolution (1 mm × 1 mm × 1 mm) to construct pial/white matter surfaces in FreeSurfer and scanned again at high resolution (120 µm × 120 µm × 120 µm) to determine cortical architectural boundaries. After labeling perirhinal area 35 in the high resolution images, we mapped the high resolution labels to the surface models to localize area 35 in fourteen cases. We validated the area boundaries determined using histological Nissl staining. To test the accuracy of the probabilistic mapping, we measured the Hausdorff distance between the predicted and true labels and found that the median Hausdorff distance was 4.0mm for the left hemispheres (n=7) and 3.2mm for the right hemispheres (n=7) across subjects. To show the utility of perirhinal localization, we mapped our labels to a subset of the Alzheimer's Disease Neuroimaging Initiative dataset and found decreased cortical thickness measures in mild cognitive impairment and Alzheimer's disease compared to controls in the predicted perirhinal area 35. Our ex vivo probabilistic mapping of the perirhinal cortex provides histologically validated, automated and accurate labeling of architectonic regions in the medial temporal lobe, and facilitates the analysis of atrophic changes in a large dataset for earlier detection and diagnosis.

NCS 613 exhibits anti-inflammatory effects on PBMCs from lupus patients by inhibiting p38 MAPK and NF-κB signalling pathways while reducing proinflammatory cytokine production.

Systemic lupus erythematosus (SLE) is a polymorphic and multigenic autoimmune disease that evolves into progressive and chronic inflammation of multiple joints and organs. Phosphorylation and activation of p38 MAPK, along with the resulting overproduction of interleukin (IL)-1ß, IL-6, and tumour necrosis factor (TNF)-α is a hallmark of inflammatory disorders. Here, we investigated the anti-inflammatory pathway modulated by NCS 613, a specific PDE4 inhibitor, on human peripheral blood mononuclear cells (PBMCs) from 5 healthy donors and 12 SLE patients. PDE4 subtypes, p38 MAPK, and IκBα protein levels were analyzed by Western blot, while NF-κB and PDE4B immunostaining was assessed in control and lipopolysaccharide (LPS) -pretreated PBMCs. Proinflammatory cytokines were quantified by ELISA, while IL-1ß mRNA was resolved by RT-qPCR. NCS 613 treatment decreased PDE4B and upregulated PDE4C in human PBMCs from healthy donors and SLE patients. LPS stimulation increased p38 MAPK phosphorylation and NF-κB translocation to the nucleus, which was abolished by NCS 613 treatment. Concomitantly, NCS 613 restored IκBα detection levels in human PBMCs from both healthy donors and SLE patients. This compound also abolished LPS-induced inflammation in PBMCs by reducing IL-6, IL-8, and TNF-α cytokines. NCS 613 is a small molecule displaying anti-inflammatory properties that may provide an alternative or complementary strategy for SLE management.

Analysis of adolescent patient satisfaction and well-being following reduction mammaplasty using the BREAST-Q survey.

BACKGROUND: While functional breast reduction surgery has been shown to lead to increased quality of life in adult patients, the effects of this operation has not been investigated as thoroughly in adolescent patients. This study uses the BREAST-Q, a validated, surgery-specific questionnaire, to measure changes in adolescent patient well-being and satisfaction following reduction mammaplasty. METHODS: All patients presenting for breast reduction consultation between February and December 2016 were asked to complete the BREAST-Q. Post-operative surveys were completed at three-month follow up. A matched control cohort was established using patients who completed a pre-operative survey and were deemed appropriate surgical candidates, but then were denied by insurance and did not undergo surgery. RESULTS: Of the 28 adolescent patients who presented for breast reduction consultation, 15 met inclusion criteria; 11 patients underwent reduction mammaplasty, and 4 patients were included in the control cohort. When these groups were compared, statistically significant improvements were observed in all BREAST-Q categories except for sexual well-being. Overall patient satisfaction correlated most highly to satisfaction with information. CONCLUSIONS: This study examines quality of life outcomes in adolescent breast reduction patients using the BREAST-Q survey. Our findings indicate that adolescent patients have an improved quality of life following breast reduction, but that their satisfaction stems from different sources from those of adult patients. Further characterization of outcomes specific to young patients with surgically managed symptomatic macromastia will increase the practice of tailored, evidence-based medicine for adolescent patients. LEVEL OF EVIDENCE: Treatment Study, Level III.

Reproducibility of the Six-Minute Walk Test in Children and Youth With Juvenile Idiopathic Arthritis.

OBJECTIVE: While the 6-minute walk test is increasingly being used in research to evaluate submaximal exercise capacity of children with juvenile idiopathic arthritis (JIA), psychometric properties with this population have not been well evaluated. We undertook this study to evaluate reproducibility (agreement and test-retest reliability) and to determine standard error of measurement (SEM) and smallest detectable difference (SDD) in children and youth with JIA. METHODS: Participants (n = 22, mean ± SD age 13.1 ± 1.1 years, 63.6% female) completed a 6-minute walk test as part of their routine clinical assessment, and then repeated the 6-minute walk test at mean ± SD 8 ± 1.2 days later, in the same clinical setting with the same rater. RESULTS: The intraclass correlation coefficient (95% confidence interval) was 0.86 (0.66-0.94); the SEM and SDD were 23.5 and 65.1 meters, respectively. CONCLUSION: These results provide evidence of good-excellent reproducibility of the 6-minute walk test with children and youth with JIA and support the use of the 6-minute walk test as a measure of submaximal exercise capacity in clinical practice and research.

Mucin production during prenatal and postnatal murine lung development.

Mucus is a protective gel that lines respiratory tract surfaces. To identify potential roles for secreted gel--forming mucins in lung development, we isolated murine lungs on embryonic days (E) 12.5-18.5, and postnatal days (PN) days 5, 14, and 28. We measured the mucin gene expression by quantitative RT-PCR, and localization by histochemical and immunohistochemical labeling. Alcian blue/periodic acid--Schiff--positive cells are present from E15.5 through PN28. Muc5b transcripts were abundant at all time points from E14.5 to PN28. By contrast, transcript levels of Muc5ac and Muc2 were approximately 300 and 85,000 times lower, respectively. These data are supported by immunohistochemical studies demonstrating the production and localization of Muc5ac and Muc5b protein. This study indicates that mucin production is prominent in developing murine lungs and that Muc5b is an early, abundant, and persistent marker of bronchial airway secretory cells, thereby implicating it as an intrinsic component of homeostatic mucosal defense in the lungs.

Strain-dependent genomic factors affect allergen-induced airway hyperresponsiveness in mice.

Asthma is etiologically and clinically heterogeneous, making the genomic basis of asthma difficult to identify. We exploited the strain-dependence of a murine model of allergic airway disease to identify different genomic responses in the lung. BALB/cJ and C57BL/6J mice were sensitized with the immunodominant allergen from the Dermatophagoides pteronyssinus species of house dust mite (Der p 1), without exogenous adjuvant, and the mice then underwent a single challenge with Der p 1. Allergic inflammation, serum antibody titers, mucous metaplasia, and airway hyperresponsiveness were evaluated 72 hours after airway challenge. Whole-lung gene expression analyses were conducted to identify genomic responses to allergen challenge. Der p 1-challenged BALB/cJ mice produced all the key features of allergic airway disease. In comparison, C57BL/6J mice produced exaggerated Th2-biased responses and inflammation, but exhibited an unexpected decrease in airway hyperresponsiveness compared with control mice. Lung gene expression analysis revealed genes that were shared by both strains and a set of down-regulated genes unique to C57BL/6J mice, including several G-protein-coupled receptors involved in airway smooth muscle contraction, most notably the M2 muscarinic receptor, which we show is expressed in airway smooth muscle and was decreased at the protein level after challenge with Der p 1. Murine strain-dependent genomic responses in the lung offer insights into the different biological pathways that develop after allergen challenge. This study of two different murine strains demonstrates that inflammation and airway hyperresponsiveness can be decoupled, and suggests that the down-modulation of expression of G-protein-coupled receptors involved in regulating airway smooth muscle contraction may contribute to this dissociation.

Hypoxia Conditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Induce Increased Vascular Tube Formation in vitro.

Mesenchymal stem/stromal cells (MSCs) display a variety of therapeutically relevant effects, such as the induction of angiogenesis, particularly under hypoxic conditions. It is generally recognized that MSCs exert their effects by secretion of paracrine factors and by stimulation of host cells. Furthermore, there is increasing evidence that some therapeutically relevant effects of MSCs are mediated by MSC-derived extracellular vesicles (EVs). Since our current knowledge on MSC-derived EVs released under hypoxic conditions is very limited, we aimed to characterize MSC-derived EVs from normoxic vs. hypoxic conditions (5% O2). Adipose-derived MSCs were grown under normoxic and hypoxic conditions, and EVs were analyzed by flow cytometry using lactadherin as a marker for EVs exposing phosphatidylserine, CD63 and CD81 as EV markers, as well as CD73 and CD90 as MSC surface markers. Particle concentration and size distribution were measured by nanoparticle tracking analysis (NTA), and the EV surface antigen signature was characterized using bead-based multiplex flow cytometry. Furthermore, we evaluated the potential of MSC-derived EVs obtained under hypoxic conditions to support angiogenesis using an in vitro assay with an hTERT-immortalized human umbilical vein endothelial cell (HUVEC) line. Proliferation and viability of MSCs were increased under hypoxic conditions. EV concentration, size, and surface signature did not differ significantly between normoxic and hypoxic conditions, with the exception of CD44, which was significantly upregulated on normoxic EVs. EVs from hypoxic conditions exhibited increased tube formation as compared to normoxic EVs or to the corresponding supernatants from both groups, indicating that tube formation is facilitated by EVs rather than by soluble factors. In conclusion, hypoxia conditioned MSC-derived EVs appear to be functionally more potent than normoxic MSC-derived EVs regarding the induction of angiogenesis.

Munc13-2-/- baseline secretion defect reveals source of oligomeric mucins in mouse airways.

Since the airways of control mouse lungs contain few alcian blue/periodic acid-Schiff's (AB/PAS)+ staining 'goblet' cells in the absence of an inflammatory stimulus such as allergen sensitization, it was surprising to find that the lungs of mice deficient for the exocytic priming protein Munc13-2 stain prominently with AB/PAS under control conditions. Purinergic agonists (ATP/UTP) stimulated release of accumulated mucins in the Munc13-2-deficient airways, suggesting that the other airway isoform, Munc13-4, supports agonist-regulated secretion. Notably, however, not all of the mucins in Munc13-2-deficient airways were secreted, suggesting a strict Munc13-2 priming requirement for a population of secretory granules. AB/PAS+ staining of Munc13-2-deficient airways was not caused by an inflammatory, metaplastic-like response: bronchial-alveolar lavage leucocyte numbers, Muc5ac and Muc5b mRNA levels, and Clara cell ultrastructure (except for increased secretory granule numbers) were all normal. A Muc5b-specific antibody indicated the presence of this mucin in Clara cells of wildtype (WT) control mice, and increased amounts in Munc13-2-deficient mice. Munc13-2 therefore appears to prime a regulated, baseline secretory pathway, such that Clara cell Muc5b, normally secreted soon after synthesis, accumulates in the gene-deficient animals, making them stain AB/PAS+. The defective priming phenotype is widespread, as goblet cells of several mucosal tissues appear engorged and Clara cells accumulated Clara cell secretory protein (CCSP) in Munc13-2-deficient mice. Additionally, because in the human airways, MUC5AC localizes to the surface epithelium and MUC5B to submucosal glands, the finding that Muc5b is secreted by Clara cells under control conditions may indicate that it is also secreted tonically from human bronchiolar Clara cells.

The polymeric mucin Muc5ac is required for allergic airway hyperreactivity.

In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and smooth muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC is an additional disease feature that, while strongly associated pathologically, is poorly understood functionally. Here we show that Muc5ac is a central effector of allergic inflammation that is required for airway hyperreactivity (AHR) to methacholine (MCh). In mice bred on two well-characterized strain backgrounds (C57BL/6 and BALB/c) and exposed to two separate allergic stimuli (ovalbumin and Aspergillus extract), genetic removal of Muc5ac abolishes AHR. Residual MCh responses are identical to unchallenged controls, and although inflammation remains intact, heterogeneous mucous occlusion decreases by 74%. Thus, whereas inflammatory effects on ASM alone are insufficient for AHR, Muc5ac-mediated plugging is an essential mechanism. Inhibiting MUC5AC may be effective for treating asthma and other lung diseases where it is also overproduced.