A 25-year-old woman with a history of pollen allergy and bronchial asthma presented with severe shortness of breath preceded by several weeks of worsening symptoms after starting a new job in a textile warehouse with high exposure to dust. The patient had been inhaling ipratropium/fenoterol several times a day over the preceding few weeks and had undergone two courses of antibiotic treatment for suspected bacterial bronchitis. Despite worsening of the symptoms, the patient had not sought attention from a specialist and had not used inhaled corticosteroids or any other medication. The past medical history included atopic eczema and pollen allergy at preschool age, with documented strong polyvalent IgE sensitization and allergic asthma treated with medium dose inhaled corticosteroids and a long-acting beta agonist at school age. In adulthood, her asthma was well-controlled, with only occasional use of relief medication. The patient had no history of hospitalization due to asthma exacerbation. She had food allergies and oral allergic syndrome triggered by nuts, apples and tomatoes, and was an occasional smoker.
Upon admission, the patient was tachypneic and complained of dry cough and breathlessness. Clinical examination revealed wheezing and tachypnea with prolonged expirium and hypoxemia, with SPO2 88% on 5 L of oxygen. Chest X-ray was normal. Status asthmaticus was diagnosed, and standard treatment with nebulized salbutamol and intravenous methylprednisolone 1000 mg was initiated. The patient was admitted to the intensive care unit, and given nebulized ipratropium/fenoterol continuously, with 2 g intravenous magnesium sulfate initially, which was then adjusted to high normal plasma level. Terbutaline 2 mg/d and theophylline 720 mg/d (monitored by drug level) were added to the therapy. A trial of noninvasive ventilation was carried out, but it was not effective. Ten hours after admission, the patient was intubated due to exhaustion and mechanical ventilation was initiated. Terbutaline was replaced with intravenous adrenalin 10 μg repeatedly at short intervals as hemodynamically tolerated, which had only a moderate effect on ventilation. Regardless of intensive bronchodilator therapy, deep sedation, muscle paralysis and an aggressive ventilatory regimen, the condition of the patient was deteriorating into severe respiratory acidosis. Therefore, support with ECMO was initiated. The respiratory acidosis was rapidly corrected and paCO2 normalized (Fig. 1). We continued treatment with methylprednisolone (1000 mg for 3 days, 60 mg from day 4), intravenous terbutaline, magnesium sulfate and theophylline. Oral montelukast 10 mg/day and intravenous bisuleptin 2 mg twice daily was added. Inhaled sevoflurane with an end-tidal concentration of 2.5% was added to ketamine (150 mg/h) and sufentanil (100 ug/h) sedation for its bronchodilatory effect. Ribavirin 600 mg twice daily, cefotaxime 2 g every 6 h and clarithromycin 500 mg twice daily were administered for 2 days until viral and bacterial lung infection was ruled out.
ECMO and ventilation parameters. Arrows show ECMO initiation on day 1 and omalizumab administration on day 7. Tidal volume and minute ventilation significantly improved within 24 h after omalizumab administration. ECMO was stopped on day 9 and the patient was extubated on day 11. ECMO, extracorporeal membrane oxygenation; Ppeak, peak inspiratory pressure; Vte expiratory tidal volume
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Echocardiogram and chest X-ray were normal, and microbiological examination of tracheal aspirate including viral and bacterial polymerase chain reaction tests were negative. Her total IgE level was hugely elevated, at 2087 kIU/L (reference range 0–150 kIU/L), with strong positivity for specific IgE against several inhaled allergens (Table 1). Her eosinophil count was normal, with an absolute value of 100/µL (reference range 0–500/µL).
Table 1 Pretreatment total and specific IgE levels
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On day 8, ventilation showed no signs of improvement despite the treatment, and the patient was still requiring full ECMO support. We administered 600 mg of omalizumab subcutaneously according to the patient’s body weight of 55 kg and the IgE level. We saw the first improvement in ventilation parameters after 90 min. Over the 12 h after omalizumab administration, the patient’s tidal volumes increased from 100 to 500 ml, minute ventilation increased from 1 to 5 L/min, and ECMO gas flow could be stopped. The following day, ECMO was disconnected. A 5-day course of meropenem was started for ventilator-associated pneumonia. Ventilation continued to improve, and the patient was weaned from sedation and mechanical ventilation, and extubated on day 10. Two weeks after the first dose, a second dose of omalizumab was administered. The patient was discharged home on day 25. Table 2 presents the results of pulmonary function tests upon discharge. Her asthma has been well controlled since hospital discharge. Oral prednisone was tapered to discontinuation, and the patient has been treated with a fixed combination of high-dose inhaled beclomethasone/formoterol, oral montelukast and levocetirizine. No additional dose of omalizumab was required.
Table 2 Pulmonary function test results upon hospital discharge
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