It doesn't always have to be OCS

Systemic corticosteroids are usually the treatment of choice for patients with chronic eosinophilic pneumonia (CEP). However, if CEP patients also suffer from other comorbidities, the adverse effects of corticosteroids should be minimized as far as possible. Doctors from Japan have now been able to report the first case of successful treatment of CEP with tezepelumab in an asthmatic woman with liver cirrhosis.

Asthma and chronic eosinophilic pneumonia can occur together, and studies have shown that oral corticosteroids (OCS) are successful in the treatment of CEP. However, it becomes difficult if the asthmatic suffers from additional comorbidities such as liver cirrhosis (LC): The metabolism of corticosteroids in the liver is impaired in patients with severe cirrhosis, and corticosteroids may further deteriorate liver function and increase the risk of impaired consciousness by increasing the amount of circulating ammonia (_NH3). For this reason, in patients with liver cirrhosis, it is a challenge to administer therapy without worsening liver function.

A 71-year-old woman presented to the team led by Professor Yasuo Shimizu, Dokkyo Medical University School of Medicine, Mibu, and first author Inaba Mizuki, Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University, Mibu, Japan, with a two-month history of productive cough, shortness of breath and hypoxia to a blood oxygen saturation (_SpO2) of 92% [1]. The respiratory symptoms were severe, with an asthma control test score of 6 points and a mean asthma control quiescence score of 5.2 points. Auscultation also revealed wheezing in both lungs.

A laboratory examination revealed normal leukocyte values of 5800 cells/μl, but an eosinophilia of 1200 cells/μl (20.7%) and a reduced platelet count (9.3 cells/μl) as well as a prothrombin activity of 66% and 3.3 g/dl albumin. Liver enzymes were high with 3.05 mg/dl total bilirubin, 1.11 mg/dl direct bilirubin, 1.94 mg/dl indirect bilirubin, 158 U/l alkaline phosphatase and 43 μg/dl ammonia. In addition, the eosinophils in the sputum were conspicuous and showed an average of 10-20 cells per field of view, measured by optical microscopy at 200x magnification in five fields.

Chest radiographs (Fig. 1) showed infiltration shadows in the right upper and lower lung fields, and computed tomography (CT) of the chest showed predominantly bilateral infiltration shadows in the upper lobes, extending to both lower lobes. CT of the sinuses revealed bilateral sinusitis. Spirometry revealed severe obstruction with a one-second capacity (_FEV1) of 0.90 l/s and a percent _FEV1 of 50.8%; fractional exhaled nitric oxide (FeNO) was 91 ppb. Bronchoscopy was not performed due to the risk of coma after anesthesia.

Rapid improvement in asthma and CEP without worsening LC

The Japanese doctors started treatment with prednisolone (10 mg/day), inhaled fluticasone furoate/vilanterol (FF/VI, 200/25 μg/day) and the TSLP inhibitor tezepelumab (210 mg/month). After 10 days, asthma symptoms improved significantly, and after one month the bilateral shadows had disappeared. Due to these improvements, the OCS dose was reduced to 3 mg/day. After two months of therapy, asthma symptoms, lung function, circulating eosinophils and FeNO levels continued to improve significantly, but _NH3 levels increased from 43 μg/dl before therapy to 75 μg/dl. Therefore, OCS was discontinued, while FF/VI and tezepelumab were continued. One month after discontinuation of OCS, the _NH3 level had returned to the initial 43 μg/dl, the other parameters and asthma symptoms remained under control without recurrence of CEP. A significant improvement was also observed in the sinusitis.

In the treatment of CEP, the recommended initial OCS dose is 0.5 mg/kg. In this case, however, the situation was complicated by uncompensated LC, the authors emphasize: the administration of OCS does more harm than good, as it worsens liver function and increases the risk of coma, infections, diabetes and gastrointestinal bleeding due to varices from the esophagus to the stomach. The initial dose of OCS was therefore reduced and biologics were used in combination.

Previous reports on the long-term safety of tezepelumab were limited to patients with non-asthmatic pulmonary eosinophilia or patients with high OCS consumption. Treatments showed no effects on liver function and no change in liver enzymes, therefore tezepelumab is considered to have a low risk of liver damage.

In addition, the Japanese patient had nasal polyps and elevated eosinophils, but the MPO-ANCA was negative. However, as there are also ANCA-negative EGPA patients, careful observation of the development of EGPA is required. In their patient, five months had passed since the discontinuation of OCS without EGPA developing during tezepelumab therapy, explain Inaba et al. The authors conclude that tezepelumab may be a treatment option for CEP and may lead to a lower risk of OCS, even in LC patients.

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