Near-Fatal Asthma Due to Severe Airway Mucus Plugging in a 12-Year-Old Boy

A 12-year-old boy was brought to the emergency department of a rural hospital due to acute shortness of breath and up to 40°C fever that had lasted for 4 days. The patient had a history of exercise-induced dyspnea without further clarification but with prescribed salbutamol (retrospectively, probably an indicative of undiagnosed asthma) and an episode of severe influenza pneumonia at the age of 3 years which was accompanied by a brief resuscitation event and 3 days of invasive ventilation. The patient was not vaccinated against influenza. Family history revealed that the patient’s mother suffered from asthma. The family originated from a socioeconomically disadvantaged background.

The patient was reported to be dyspneic with expiratory wheezing and the initial peripheral oxygen saturation was 80%, so that he was admitted to a pediatric ward. The initial infection parameters were within the normal range and the polymerase chain reaction (PCR) from a nasal swab confirmed an influenza B infection. Chest radiography revealed right upper lobe atelectasis, right-sided pneumothorax, and soft tissue emphysema (see [Fig. 1a]). High-flow therapy, prednisolone and inhalation of salbutamol were started. Due to rapid deterioration, anti-obstructive therapy was escalated with magnesium and continuous administration of reproterol and esketamine. Nevertheless, intubation and chest drainage became necessary and he was subsequently transferred to our pediatric intensive care unit (PICU).

Fig. 1 (a) A chest radiograph and (b) a CT scan on admission showing right upper lobe atelectasis, mediastinal and soft tissue emphysema, airway wall thickening and mucus plugging of the entire tracheobronchial tree extending into the lung periphery, indwelling tube and pleural drainage. (c) An enlarged view of the peripheral mucus plugs in the CT image (marked with arrows) and the airway wall thickening (marked with asterisks). (d) Bronchoscopically retrieved pulmonary cast. (e) A chest X-ray showing white lungs and additional ECMO cannulas 2 days after hospital admission. CT, computed tomography.

At admission to our PICU, we saw a critically ill patient with auscultatory silent chest and a severely impaired gas exchange with an oxygenation index (OI) of 24, a PaCO₂ of 74 mm Hg, and an arterial pH of 7.2, despite highly invasive mechanical ventilation with a peak pressure of 46 mbar, a positive end-expiratory pressure of 10 mbar and a resulting tidal volume (TV) of 3.8 ml/kg PBW met the criteria for severe pediatric acute respiratory distress syndrome (ARDS; Emeriaud, G et al., Pediatr Crit Care Med. 2023;24(2):143–168). By adjusting ventilation, intensifying anti-obstructive therapy and muscle relaxation, stabilization at a low level was achieved (PaCO₂: 49 mmHg and OI: 14). CT imaging demonstrated complete atelectasis distal of the obstructed right upper lobe bronchus and extensive mediastinal emphysema, as well as severe mucus plugging of the entire tracheobronchial tree (see [Fig. 1b/c]). Several large pulmonary casts were removed from the right upper lobe bronchus during subsequent bronchoscopy (see [Fig. 1d]). However, the peripheral sections of the tracheobronchial tree remained congested with mucus and the lung function continued to deteriorate, as there are currently no effective mucolytics available for treatment. Ultimately, in accordance with current PARDS guidelines (Rambaud, J et al., Pediatric critical care medicine 2023; S124–S134), the patient had to be cannulated for a high-flow veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a bridge-to-recovery strategy due to an almost completely impaired mechanical ventilation with a TV of only 2 mL/kg PBW and severe hypercapnia (PaCO₂: 130 mm Hg).

The following day, despite V-V ECMO, the patient suffered from desaturation and hemodynamic collapse due to further deterioration of the lung function and complete bilateral lung opacities as a radiological correlate of ARDS (see [Fig. 1d]). Noteworthy, sufficient oxygenation could only be achieved by improving the ratio of ECMO blood flow to cardiac output with heart rate control by temporarily stopping anti-obstructive therapy and further optimization of the hemodynamic situation by therapy of secondary pulmonary arterial hypertension (38 mmHg plus central venous pressure) with enoximone and sildenafil.

Mucus clearing and pulmonary recruitment were achieved through repeated therapeutic prone positioning, restarting of prednisolone (which was paused before ECMO initiation for infectious considerations), daily bronchoscopies with the removal of abundant thick mucus under secretolytic therapy, vibration therapy and physiotherapy. Due to recurrent bronchospasms and sedation intolerance, volatile sedation with sevoflurane was established for 4 days. As anti-infective therapy, the patient received oseltamivir and empirical antibiotic therapy to treat a possible bacterial superinfection. Initial extubation after 12 days failed due to insufficient secretion mobilization and agitation with tachydyspnea. With modified delirium therapy, as well as intensive anti-obstructive inhalation therapy, successful extubation was achieved after a total of 14 days of invasive ventilation. After further 3 days of weaning from ECMO blood and gas flows, the patient was decannulated from ECMO.

In addition to the severe mucus plugging apparent on chest CT, the airway casts removed during the first bronchoscopy appeared impressive. Severe airway mucus plugging of the entire tracheobronchial tree is a rare event, but has been reported in patients with fatal asthma assumingly resulting from massively increased secretion of mucins (MUC5AC and MUB5B) in combination with acutely impaired mucociliary clearance (Kuyper LM et al., Am J Med 2003;115(1):6–11). This is in line with our observation of a substantial increase in the mucus percent solids of 18.9% in the mucus cast, which was more than six times higher compared to healthy airway mucus that contains up to 3% solids (Fahy J et al., N Engl J Med 2010;363:2233–2247). The mechanisms of plug formation and persistence remain poorly understood and no mucolytic therapies are available for targeted therapy (Liegeois MA et al., J Clin Invest 2025;135(6):e186889 and Zhou-Suckow Z et al., Cell Tissue Res 2017;367(3):537–550). The development of effective mucolytic therapies therefore remains a high unmet need (Addante A et al., Eur Respir J. 2023;25;61(5):2202022). Airway casts are also the main feature of bronchitis plastica, which is a rare condition and known to be associated with pulmonary, mostly inflammatory disorders and cardiovascular diseases mainly after palliatively corrected malformations with a functionally univentricular heart. The latter was ruled out in our patient by anamnesis and echocardiography. (Kreuter M et al., Seltene Lungenerkrankungen. 2. Aufl. Springer 2022; 577–582). Additional diagnostics were performed to assess potential risk factors of the severe course of the disease. Due to the second severe pulmonary failure associated with influenza infection, we performed immunological work-up which revealed normal differential including T- and natural killer cell counts, vaccination titers, and complement. Specifically, interferon (IFN) autoantibodies were not detected, and monocytic HLA-DR expression normalized after discontinuation of steroids. Trio whole-genome sequencing, which analyzed in detail known influenza-associated genes (e.g., type I/III IFN/TLR and inflammasome genes), as well as respiratory epithelial signaling pathways for mucus production, transport, and barrier functions (including CFTR and PCD genes), did not reveal any pathological variant known to date. However, an influenza-specific functional defect cannot be entirely excluded given the clinical phenotype.

Known related diseases to pulmonary casts were evaluated in our patient: there was no evidence of bacterial or fungal pneumonia in the microbiological cultures and PCR. Among respiratory viruses, only influenza type B was detected. Cystic fibrosis or primary ciliary dyskinesia could be genetically ruled out. Furthermore, trio exome sequencing did not reveal any significant findings. The diagnosis of a severe asthma attack triggered by influenza infection as the underlying cause of severe mucus plugging is supported by eosinophilia in blood and bronchoalveolar lavage. Further indicators of atopy were a significantly elevated IgE level (3442 kU/L) and sensitization to birch pollen (CAP class 6). In addition, pulmonary function testing revealed mild obstructive ventilation disorder (a percent predicted forced expiratory volume of 77%). Exhaled nitric oxide (FeNO) was within normal limits (20 ppb), but this was most likely influenced by glucocorticoid therapy; after 3 months, the FeNO rose to 82 ppb under step 6 (NVL) anti-asthmatic therapy with inhaled corticosteroids (ICS), long-acting β₂-agonists (LABA) and dupilumab. In summary, these findings are consistent with a diagnosis of near-fatal asthma, probably triggered by the influenza infection due to airway mucus plugging.

In line with this hypothesis, histological examination of the mucus plugs revealed abundant eosinophils and Charcot-Leyden crystals (CLC; see [Fig. 2a/b]). The latter are extracellular bipyramidal crystals and consist of galectin-10, a protein that occurs in large quantities in the cytoplasm of eosinophils and is considered a marker for tissue eosinophilia in type 2 inflammation (Aegerter et al. Curr Opin Immunol 2021;72:72–78). However, recent research has identified CLC as not only a marker but also a driver of type 2 airway inflammation and asthma development (Persson EK et al. Science 2019;364,6442: eaaw4295). Treatment options of severe type 2 inflammation include corticosteroids and biologicals targeting key type 2 signaling pathways, such as IL-4/IL-13 signaling, e.g., with dupilumab targeting the common interleukin (IL)-4/IL-13 receptor (Venegas G et al., Allergology international: official journal of the Japanese Society of Allergology 2024; 73,3: 351–361). Blood eosinophilia in our patient decreased dramatically under systemic corticosteroid therapy (see [Fig. 2c]). On day 18, we started treatment with dupilumab, which has been shown to reduce mucus and improve ventilation (Svenningsen S et al., Am J Respir Crit Care Med 2023;208(9):995–997), allowing the tapering of systemic glucocorticoids. Furthermore, continuous inhalation therapy with ICS and LABA was initiated, and after 31 days the patient was discharged from hospital for a regular follow-up of this asthma and will receive an annual influenza vaccination.

Fig. 2 Eosinophils at manifestation and after initiation of therapy. (a and b) Eosinophils and Charcot-Leyden-Crystals in histopathological examination of the (a) BAL (native) and (b) mucus cast (H&E). (c) Eosinophils in BAL (dashed line), and eosinophils in blood (solid line) under administered medication. BAL, bronchoalveolar lavage; DP, dupilumab; GC, systemic glucocorticoids.

In conclusion, we report an exceptional case of near-fatal asthma due to severe mucus plugging that cannot be resolved through medication or interventional therapies in a 12-year-old boy who has several key risk factors of a fatal asthma attack in children identified in a recent meta-analysis, including previous hospitalization, low socioeconomic status, allergies, prescription of asthma medications, history of pneumonia, rural location, adolescence, and paternal asthma (Gawlik-Lipinski A et al., Pediatr Pulmonol 2025; 60(8):e71255), but had no treatment or follow-up for his pre-existing but unrecognized asthma.

In brief, three main points of clinical significance are highlighted by this case:

• This case highlights the role of severe airway mucus plugging in near-fatal asthma with ARDS in children.

• In these cases, early chest CT imaging should be considered to evaluate the severity of mucus plugging, and the early use of dupilumab may be considered to reduce mucus hypersecretion in type 2 inflammation.

• In cases where mechanical ventilation is insufficient, veno-venous ECMO provides a therapeutic option to bridge patients with near-fatal asthma until mucus plugging has resolved.

• Children with known risk factors of fatal asthma need to be followed regularly to ensure asthma control.

Publication History

Article published online:
10 February 2026