Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma.

BACKGROUND: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain. OBJECTIVE: We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma. METHODS: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3. RESULTS: Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (rs values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/µL and 42% of participants with blood eosinophil counts between 150 and 299 cells/µL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized. CONCLUSIONS: Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation.

[Modeling T2 high severe asthma using human induced pluripotent stem cells (hiPSC)]. / Modélisation de l'asthme sévère par la technologie des cellules humaines souches pluripotentes induites (hiPSC).

Severe asthma patients with persistent airflow obstruction are characterized by functional obstruction due to mucus plugs containing mucins, fibrin, and eosinophil derived Charcot- Leyden crystals. The molecular mechanisms underlying this endotype are not clearly understood. Developing new models is crucial to respiratory research insofar as critical differences exist between human and rodent airway epithelium. We (and other teams) have shown that it is possible to reconstitute in vitro a complex and functional airway epithelium displaying all the features described in vivo from human-induced pluripotent stem cells (hiPSC). Our aim is to establish a human in vitro model of severe asthma that will recapitulate airway epithelium remodeling and mucus plugs.

MDCT and MRI in Bronchiectasis in Older Children and Young Adults - A Non-Inferiority Trial.

OBJECTIVES: To compare and evaluate the usefulness of magnetic resonance imaging (MRI) with computed tomography (CT) in bronchiectasis; to compare MRI and CT scores with pulmonary function tests (PFT) and to evaluate the role of Diffusion-weighted imaging (DWI) in bronchiectasis. METHODS: In this prospective study, 25 patients between 7-21 y of age with a clinical/radiological diagnosis of bronchiectasis underwent MDCT and MRI chest. MRI and CT scoring was performed using modified Bhalla-Helbich's score by two independent radiologists for all parameters. A final consensus score was recorded. The overall image quality of different MRI sequences to identify pathologies was also assessed. Appropriate statistical tests were used for inter-observer agreements, and correlation amongst CT and MRI; as well as CT, MRI and PFT. RESULTS: Strong agreement (ICC 0.80-0.95) between CT and MRI was seen for extent and severity of bronchiectasis, number of bullae, sacculation/abscess, emphysema, collapse/ consolidation, mucus plugging, and mosaic perfusion. Overall CT and MRI scores had perfect concordance (ICC 0.978). Statistically significant (p-value <0.01) intra-observer and inter-observer agreement for all CT and MRI score parameters were seen. A strong negative correlation was seen between total CT and MRI severity scores and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF) 25-75%. DWI MR, with an apparent diffusion coefficient (ADC) cut-off of 1.62 × 10-3 mm3/s had a sensitivity of 70% and specificity of 75% in detecting true mucus plugs. CONCLUSIONS: MRI with DWI can be considered as a radiation-free alternative in the diagnostic algorithm for assessment of lung changes in bronchiectasis, especially in follow-up.

Imaging Regional Airway Involvement of Asthma: Heterogeneity in Ventilation, Mucus Plugs and Remodeling.

The imaging of asthma using chest computed tomography (CT) is well-established (Jarjour et al., Am J Respir Crit Care Med 185(4):356-62, 2012; Castro et al., J Allergy Clin Immunol 128:467-78, 2011). Moreover, recent advances in functional imaging of the lungs with advanced computer analysis of both CT and magnetic resonance images (MRI) of the lungs have begun to play a role in quantifying regional obstruction. Specifically, quantitative measurements of the airways for bronchial wall thickening, luminal narrowing and distortion, the amount of mucus plugging, parenchymal density, and ventilation defects that could contribute to the patient's disease course are instructive for the entire care team. In this chapter, we will review common imaging methods and findings that relate to the heterogeneity of asthma. This information can help to guide treatment decisions. We will discuss mucous plugging, quantitative assessment of bronchial wall thickening, delta lumen phenomenon, parenchymal low-density lung on CT, and ventilation defect percentage on MRI as metrics for assessing regional ventilatory dysfunction.

Reduced serum 25(OH)D is closely related to bronchial mucus plug formation in children with mycoplasma pneumonia: A prospective cohort study.

Background: The relationship between vitamin D nutritional status and the formation of bronchial mucus plugs (BMPs) is unclear. The aims of the current study were to investigate associations between serum 25(OH)D levels, serum inflammatory factors, and clinical characteristics in children with mycoplasma pneumonia (MPP), and to summarize the risk factors for BMPs in children with MPP. Methods: Clinical data from 175 children with MPP were collected and analyzed, the children were divided into a BMP group and a non-BMP group. Serum 25(OH)D levels, IL-8, and various inflammatory factors were compared in the two groups. Associations between 25(OH)D levels and IL-8, various inflammatory factors, and clinical characteristics were analyzed, and the diagnostic value of serum 25(OH)D levels was assessed. Results: Serum 25(OH)D level was significantly lower in the BMP group (p < 0.05). Serum IL-8 level, percentages of neutrophils, and some inflammatory factors were significantly higher in the BMP group (p < 0.05). Serum 25(OH)D level was negatively correlated with IL-8, neutrophil percentage, various inflammatory factors (all p < 0.05). It was also associated with lobular infection, pleural effusion, mechanical ventilation, and mycoplasma 2,063/2,064 mutation (all p < 0.05). In multivariate regression analysis 25(OH)D [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.97-0.99, p = 0.003], IL-8 (OR 1.02, 95% CI 1.00-1.04, p = 0.002), polylobular infection (OR 1.75, 95% CI 1.17-2.64, p = 0.007), and MP DNA copies (OR 0.98, 95% CI 1.04-1.01, p = 0.022) were independent risk factors for BMPs, and the area under the curve value was 0.915 (95% CI 0.895-0.935). If the serum 25(OH)D level was <50 nmol/L, the respective percentages for sensitivity, specificity, positive predictive value, and negative predictive value were 97, 81, 78.9, and 97.6%. Conclusions: Vitamin D deficiency is common in children with MPP, and 25(OH)D levels are closely associated with inflammatory factors and disease severity in children. The serum 25 (OH) D level of MPP children with BMPs was lower than that of children without BMPs. Serum 25(OH)D can be used as a marker for the diagnosis of MPP in children with BMPs.

Successful treatment with dupilumab for mucus plugs in severe asthma.

A 29-year-old man presented to our hospital with severe eosinophilic asthma. He needed a short OCS burst for exacerbation of asthma once every 1 or 2 months, although he used a high dose of inhaled corticosteroids and a long-acting beta-2 agonists. Chest CT showed multiple mucous plugs with bronchiectasis, but further examination found that he did not meet the diagnostic criteria for allergic bronchopulmonary aspergillosis. After starting dupilumab for his severe eosinophilic asthma, his asthma control improved without exacerbation. Furthermore, most mucus plugs disappeared on chest CT after 16 weeks from initiating dupilumab. This case suggests that dupilumab may be an effective treatment against mucus plugs associated with severe eosinophilic asthma.

Luminal mucus plugs are spatially associated with airway wall thickening in severe COPD and asthma: A single-centered, retrospective, observational study.

BACKGROUND: Airway wall thickening and excess airway mucus occur in asthma and chronic obstructive pulmonary disease (COPD), but few studies have investigated the relationship between them. Our objective was to determine the association between computed tomography (CT) airway wall thickening in segmental airways proximal to airways with or without mucus plugging in patients with asthma and COPD. METHODS: Mucus plugging was scored using a CT bronchopulmonary segment-based scoring system in asthma and COPD patients. For each of the 19 segmental airways, a mucus plug was defined as complete occlusion of one or more of the daughter branches (sub-segmental airways) by mucus. CT airway measurements were generated for each of the 19 segmental airways: wall-area-percentage (WA%), lumen area (LA), and total airway count (TAC) (VIDA Diagnostics Inc.). Multivariable logistic regression models were constructed for the presence of mucus plugs with corresponding CT measurement and adjusted by covariates; each of the 19 segments was treated as a nested variable. RESULTS: A total of 33 participants were evaluated. Participants had a mean age of 60 ± 15yrs and there were n = 14 (42%) males. There were 16 (48%) participants with a diagnosis of asthma and 17 (52%) with a COPD diagnosis. The mean FEV1 was 53 ± 21%pred and FEV1/FVC was 54 ± 15%. The mean mucus score in all participants was 15 ± 4 (min = 0, max = 19). Multivariable logistic regression analysis showed the presence of airway mucus was significantly associated with increased CT WA% (ß = 7.30, p = 0.004) and reduced TAC (ß = -0.06, p = 0.045). CONCLUSIONS: There was increased airway wall thickness and reduced airway counts on CT in segments where there was a distal mucus plug compared to segments without mucus plugs in asthma and COPD.

Mucus plugs in peripheral bronchi: An unusual initial manifestation of allergic bronchopulmonary aspergillosis.

Although allergic bronchopulmonary aspergillosis can be associated with mucus plugs in the central bronchi, this association in the peripheral bronchi remains unclear. A 78-year-old woman presented with mucus plugs in both the peripheral and the central bronchi in the right lung, which evolved into consolidation with high-attenuation mucus after one month.

Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time.

Rationale: Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. Objectives: To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. Methods: In a longitudinal analysis of baseline and Year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time. Changes in mucus plug score were analyzed in relation to changes in lung function and CT air trapping measures. Measurements and Main Results: In 164 participants, the mean (range) mucus plug score was similar at baseline and Year 3 (3.4 [0-20] vs. 3.8 [0-20]). Participants and bronchopulmonary segments with a baseline plug were more likely to have plugs at Year 3 than those without baseline plugs (risk ratio, 2.8; 95% confidence interval [CI], 2.0-4.1; P < 0.001; and risk ratio, 5.0; 95% CI, 4.5-5.6; P < 0.001, respectively). The change in mucus plug score from baseline to Year 3 was significantly negatively correlated with change in FEV1% predicted (rp = -0.35; P < 0.001) and with changes in CT air trapping measures (all P values < 0.05). Conclusions: Mucus plugs identify a persistent asthma phenotype, and susceptibility to mucus plugs occurs at the subject and the bronchopulmonary segment level. The association between change in mucus plug score and change in airflow over time supports a causal role for mucus plugs in mechanisms of airflow obstruction in asthma.

Progress of airway mucus plugs in bronchial asthma / 国际儿科学杂志

Mucus plugs is a feature of fatal asthma, which is the abnormally thick mucus accumulated in the airway of patients.The study of airway mucus plugs in asthmatic patients began 100 years ago.In addition to the manifestation of primary disease, asthma patients with mucus plugs may have acute exacerbation of asthma or poor treatment effect.At this time, we should pay attention to the existence of mucus plugs.Multidetector computed tomography can be used to identify and evaluate mucus plugs.This article briefly describes the generation of airway mucus, and introduces the formation mechanism, clinical characteristics, identification and scoring system of mucus plugs in asthmatic patients, and reviews the differential diagnosis and treatment of mucus plugs.

Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome.

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.

Mucus Hypersecretion and Ciliary Impairment in Conducting Airway Contribute to Alveolar Mucus Plugging in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease attributed to the complex interplay of genetic and environmental risks. The muco-ciliary clearance (MCC) system plays a critical role in maintaining the conduit for air to and from the alveoli, but it remains poorly understood whether the MCC abnormalities in conducting airway are involved in IPF pathogenesis. In this study, we obtained the surgically resected bronchi and peripheral lung tissues from 31 IPF patients and 39 control subjects, and we sought to explore the morphologic characteristics of MCC in conducting airway by using immunostaining and scanning and transmission electron microscopy. In the submucosal regions of the bronchi, we found that the areas of mucus glands (MUC5B+) were significantly larger in IPF patients as compared with control subjects (p < 0.05). In the surface epithelium of three airway regions (bronchi, proximal bronchioles, and distal bronchioles), increased MUC5B and MUC5AC expression of secretory cells, decreased number of ciliated cells, and increased ciliary length were observed in IPF patients than control subjects (all p < 0.05). In addition, the mRNA expression levels of MUC5B were up-regulated in both the bronchi and peripheral lung of IPF patients than those of control subjects (p < 0.05), accompanied with 93.55% IPF subjects who had obvious MUC5B+ mucus plugs in alveolar regions. No MUC5B rs35705950 single-nucleotide polymorphism allele was detected in both IPF patients and control subjects. Our study shows that mucus hypersecretion and ciliary impairment in conducting airway are major causes of mucus plugs in alveolar regions and may be closely related to the alveolar injuries in IPF patients.

New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation.

BACKGROUND: There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available. OBJECTIVE: This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods. METHODS: Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n = 37), chronic eosinophilic pneumonia (n = 64), Aspergillus-sensitized severe asthma (n = 26), or chronic pulmonary aspergillosis (n = 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey. RESULTS: The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively. CONCLUSIONS: The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.

Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

Rationale: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD.Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression.Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV1 and peripheral oxygen saturation (P < 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (P < 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute-walk distance (329 ± 115 vs. 392 ± 117 m) (P < 0.001).Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Predictive factors of refractory Mycoplasma pneumoniae pneumonia / 中华实用儿科临床杂志

Mycoplasma pneumoniae is one of the common causes of community-acquired pneumonia in preschool and school-age children.Although it is self-limited in some children, there are still some cases of refractory Mycoplasma pneumoniae pneumonia(RMPP), which are characterized by various intrapulmonary and extrapulmonary complications, such as the formation of bronchial mucus plugs, necrotizing pneumonia and so on, and even endanger the lives of children.In recent years, with the increase of morbidity of RMPP, some studies have shown that early use of corticosteroids can significantly relieve its clinical symptoms and improve prognosis.Therefore, it is essential to understand the pathogenesis of Mycoplasma pneumoniae pneumonia, identify the high risk factors for predicting RMPP and its associated complications, and then formulate relevant prediction scales.

Airway microbiota in children with bronchial mucus plugs caused by Mycoplasma pneumoniae pneumonia.

BACKGROUND: There is increasing evidence for a role of lung microbiota in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). However, the alterations of lung microbiota in MPP with bronchial mucus plugs and its role in disease pathogenesis remain poorly understood. METHODS: In this prospective observational study, we performed a longitudinal 16S rRNA-based microbiome survey on bronchoalveolar lavage (BAL) samples collected from 31 MPP with bronchial mucus plugs and 52 MPP without mucus plugs. RESULTS: Our study showed a clear difference in airway microbiota between MPP children with and without bronchial mucus plugs. The MPP children with mucus plugs had lower abundances of Sphingomonas and Elizabethkingia, and a high abundance of Mycoplasma compared with MPP children without mucus plugs, subsequently contributing to increased ratios of Mycoplasma to Sphingomonas and Mycoplasma to Elizabethkingia. Children's age, fever time and serum cytokine levels were associated with airway microbiota alteration. Furthermore, significant correlations between bacterial genus abundances were found in MPP children with mucus plugs. CONCLUSIONS: Our results suggest an impact of airway microbiota on the clinical course of MPP in children, deserving further investigations.

CT and Functional MRI to Evaluate Airway Mucus in Severe Asthma.

BACKGROUND: Intraluminal contributor(s) to airflow obstruction in severe asthma are patient-specific and must be evaluated to personalize treatment. The occurrence and functional consequence of airway mucus in the presence or absence of airway eosinophils remain undetermined. OBJECTIVE: The objective of this study was to understand the functional consequence of airway mucus in the presence or absence of eosinophils and to identify biomarkers of mucus-related airflow obstruction. METHODS: Mucus plugs were quantified on CT scans, and their contribution to ventilation heterogeneity (using MRI ventilation defect percent [VDP]) was evaluated in 27 patients with severe asthma. Patients were dichotomized based on sputum eosinophilia such that the relationship between mucus, eosinophilia, and ventilation heterogeneity could be investigated. Fractional exhaled nitric oxide (Feno) and related cytokines in sputum were measured. RESULTS: Mucus plugging was present in 100% of asthma patients with sputum eosinophils and 36% of those without sputum eosinophils (P = .0006) and was correlated with MRI VDP prebronchodilator (r = 0.68; P = .0001) and postbronchodilator (r = 0.72; P < .0001). In a multivariable regression, both mucus and eosinophils contributed to the prediction of postbronchodilator MRI VDP (R2 = 0.75; P < .0001). Patients with asthma in whom the mucus score was high had raised Feno (P = .03) and IL-4 (P = .02) values. Mucus plugging correlated with Feno (r = 0.63; P = .005). CONCLUSIONS: Both airway eosinophils and mucus can contribute to ventilation heterogeneity in patients with severe asthma. Patients in whom mucus is the dominant cause of airway obstruction have evidence of an upregulated IL-4/IL-13 pathway that could be identified according to increased Feno level.

Independent predictors for longer radiographic resolution in patients with refractory Mycoplasma pneumoniae pneumonia: a prospective cohort study.

OBJECTIVES: To examine prospectively the radiographic clearance of refractory Mycoplasma pneumoniae pneumonia (RMPP) in immunocompetent children, and to identify independent predictors of time to complete radiographic resolution in patients with RMPP. DESIGN: A prospective cohort study. SETTING: Children's Hospital of Soochow University, China. PARTICIPANTS: A total of 187 patients with RMPP treated with bronchoscopy were prospectively enrolled in the study between January 2012 and December 2015. METHODS: Serial chest radiographs were obtained after discharge every 4 weeks up to a maximum of 24 weeks after diagnosis or until large infiltration on chest radiographs had resolved. Multivariate logistic regression was performed to identify independent predictors of time to complete radiographic resolution. RESULTS: Of the 187 patients with RMPP, bronchial mucus plug formation was detected in 73 (39.0%). C reactive protein (CRP) ≥50 mg/L, lactate dehydrogenase (LDH) ≥480 U/L, total fever duration ≥10 days and presence of mucus plugs were associated with longer time to radiographic clearance (all p<0.01). Compared with children without mucus plugs, those with mucus plugs were significantly more likely to have longer time to radiographic clearance (adjusted OR: 11.5; 95% CI 2.5 to 45.7; p<0.01). CONCLUSION: Clinicians might use duration of fever, CRP, LDH and presence of mucus plugs as parameters to identify children at a longer time to radiographic clearance in patients with RMPP.