Plastic Bronchitis in Sickle Cell Disease, Asthma, and Acute Infection: “The Perfect Storm”?

To the Editor, In 2019, prior to the COVID-19 pandemic, a 7-year-old male child known to have sickle cell disease (SCD)—on daily hydroxyurea, folate and penicillin V—presented with a 2-day history of cough, fever, and difficulty in breathing. On examination he was febrile (38.4°C), with oxygen saturations at 78% in room air, increasing to 92% on high flow oxygen. He was well-nourished and had features of atopy. Notably his left hemithorax was dull to percussion and had reduced air entry. Crepitations were auscultated bilaterally. Investigations revealed an elevated white blood cell (WBC) count of 42,250 per microliter, predominantly neutrophilic (36,210 per microliter) with a normal eosinophil count (326 per microliter), raised C-reactive protein (CRP) of 122 mg/L, and low hemoglobin of 9 g/dL. Chest radiography showed an opacified left hemithorax (Figure 1A). We entertained a diagnosis of acute chest syndrome (ACS) with a left pleural effusion however the drain was not active after chest tube insertion. Chest computed tomography (CT) revealed complete consolidation of the left upper and lower lobes with multifocal right lung consolidation (Figure 1B), and a small right pleural effusion. The child was admitted to the intensive care unit and commenced on intravenous high-dose ceftriaxone, amikacin, and maintenance fluids. Over the next 72 h he developed clinical features of heart failure with more prominent pallor and remained febrile but alert on nasal continuous positive airway pressure. His hemoglobin had fallen to 6 g/dL and CRP risen to 130 mg/L. Lactate dehydrogenase was elevated at 1000 IU/L. Other liver function, renal function, and coagulation parameters were unremarkable. Echocardiography was normal. Abdominal ultrasound revealed hepatomegaly but no other organomegaly, lymphadenopathy, masses or complications. Molecular testing for respiratory viruses and atypical bacteria was not available. Urine and pleural fluid cultures were negative. He had no central lines, but his blood culture was positive for Staphylococcus epidermidis, sensitive to vancomycin/erythromycin. We administered packed cell transfusions, initiated diuretics with strict input-output monitoring, and changed his antibiotics to meropenem and vancomycin. Plastic bronchitis was suspected based on the child's persistent localized respiratory findings and review of chest CT images. Combined 3% hypertonic saline/salbutamol/heparin nebulization, twice daily chest physiotherapy, and incentive spirometry (Figure 1C) were initiated. Empiric azithromycin and fluconazole were added for atypical and fungal cover as he was spiking fevers despite being on meropenem and vancomycin for 72 h. We confirmed plastic bronchitis on flexible bronchoscopy. White endobronchial plugs seen throughout the left bronchial tree were suctioned (Figure 1D). Cytology of the endobronchial plugs and serum immunoglobulin E levels were not performed. The patient's clinical condition and interval chest radiography 72-h after bronchoscopy showed marked improvement (Figure 1E); CRP dropped to 20.2 mg/L; WBC count normalized to 9200 per microliter, and hemoglobin was 11.2 g/dL. Broncho-alveolar lavage cultures were negative. He remained afebrile and completed 10 days of meropenem-vancomycin. Oxygen saturations improved to 96% in room air. He was discharged home to complete his therapeutic azithromycin/fluconazole course, continue incentive spirometry, daily inhaled budesonide, and salbutamol when necessary. Chest radiography at his 6-week review after discharge showed near-complete resolution (Figure 1F). Since discharge, the child has had three hospitalizations related to painful crises/infection: none due to a respiratory exacerbation. His clinical examination in October 2024 at his pulmonology review was unremarkable except for allergic rhinitis. The latest chest radiograph revealed no consolidations; however, new prominent vascular markings were noted (Figure 1G). He had a normal prebronchodilator spirometry analyzed using race-neutral reference equations. Postbronchodilator spirometry revealed an increase of 15% of his predicted forced vital capacity, classified as a significant bronchodilator response (> 10%). Skin prick testing on a limited aeroallergen panel comprising Dermatophagoides pteronnyssinus, Dermatophagoides farinae, Aspergillus fumigatus, Dog, Cat, German cockroach, and grass mix did not indicate any sensitization. Follow up transthoracic echocardiography revealed a structurally normal heart study with no evidence of pulmonary hypertension. Notably, tricuspid regurgitation was trivial with a maximum gradient of 21 mmHg, and tricuspid annular plane systolic excursion measured with M-Mode was 37 mm (> 18 mm)—normal parameters. The child is scheduled to continue outpatient clinic follow-up with haematology, pulmonology, and cardiology teams. Why do some children with SCD, atopy/asthma or acute infection get plastic bronchitis—a rare condition characterized by endobronchial plugs that form bronchial casts? Could the combination of these three factors, an “unhappy triad,” result in the perfect storm? What is the optimal treatment for plastic bronchitis in children with comorbid SCD, asthma and acute infection? To our knowledge, we describe the first documented case of plastic bronchitis in a child with ACS in an African context [1]. Case reports on plastic bronchitis in children with SCD are limited [1, 2]. Plastic bronchitis has been described in asthma including a report of a Kenyan child with atopy [3]. Although pediatric SCD-asthma comorbidity is prevalent, data on plastic bronchitis in children with SCD-asthma/atopy are scarce. It is possible that children with plastic bronchitis in SCD go undiagnosed, and may be classified as severe pneumonia/ACS or die [2]. Respiratory viruses including adenovirus, influenza and human bocavirus, and atypical bacteria like Mycoplasma pneumoniae have also been implicated in plastic bronchitis [4]. It is probable that our patient had a coinfection with an atypical bacterium given their prompt response to macrolide therapy, however molecular testing was not available at the time. It is not clear if there are modifying genes that are associated with this severe disease presentation, and to what extent comorbid SCD, asthma/atopy and acute infections contribute to plastic bronchitis, creating the perfect storm. Bronchoscopy is integral in plastic bronchitis management as it is diagnostic and therapeutic [3]. Advanced technologies including cryotherapy are useful tools in an interventional pulmonologist's armamentarium particularly in extracting endobronchial plugs/foreign bodies and are now available in Kenya. We did not evaluate our patient's endobronchial plug cytology to classify the disease. Eosinophilic plastic bronchitis was most plausible in our patient as he had features of atopy and was managed for comorbid asthma. Despite plastic bronchitis being an ultra-rare condition, optimal treatment adjuncts to endobronchial plug/cast removal including nebulised heparin, dornase, hypertonic saline, salbutamol and their combinations need to be studied comprehensively. Mepolizumab has been used in one case report of eosinophilic plastic bronchitis with a successful outcome; and bronchial airway eosinophils were used to monitor treatment response [5]. Exploring the use of eosinophils as a biomarker to predict SCD exacerbations and avert ACS/plastic bronchitis utilizing less invasive respiratory airway samples like induced sputum may be useful. Larger trials on the effectiveness of incentive spirometry to prevent ACS as a proxy of plastic bronchitis are needed [6], particularly in children. A high index of clinical suspicion in our patient prompted timely diagnostic and interventional bronchoscopy coupled with intensive hypertonic saline/salbutamol/heparin nebulization and incentive spirometry, leading to an optimal clinical outcome. We report this case to alert health workers in our context that plastic bronchitis in ACS occurs in the African setting and can have a good outcome if recognized early and managed promptly. Further research is needed to understand the underlying triggers of plastic bronchitis in patients with sickle cell disease, and consequently investigate evidence based preventive strategies to avoid this potentially fatal complication. Questions still abound, is it an immune failure to clear infection well like in early-stage pulmonary alveolar proteinosis? Is this dependant on a person's genetic predisposition? Is it courtesy of the aggressive infectious agent? Whatever the reason, more research is needed in this area to guide treatment. Diana Marangu-Boore: conceptualization, writing–original draft, visualization, writing–review and editing, investigation, data curation, resources, project administration. George Nyale: investigation, visualization, writing–review and editing, supervision, conceptualization. We wish to thank the parents and all individuals involved in the care of this patient. The authors received no specific funding for this work. We obtained written assent from the child and written informed consent from his parent. We also received ethical approval from the Kenyatta National Hospital/University of Nairobi Ethics Research Committee (KNH-ERC/01/PUB/5) for publication of this case report. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.