Drug-associated Interstitial Lung Disease Research Articles

Severe interstitial lung disease following treatment with certolizumab pegol: a case report

To the Editor: Over the past decade, the understanding of autoimmune diseases and the development of biological agents have radically changed the treatment paradigm for severe rheumatoid arthritis. Several tumour necrosis factor (TNF)-α inhibitors are available for clinical use, relieving symptoms and reducing the likelihood of relapse in patients not responding successfully to disease-modifying antirheumatic drugs; however, there are limited data regarding the safety of, in particular the newest, TNF-α inhibitor. Drug-associated interstitial lung disease is a well-known serious and potentially fatal adverse effect of early TNF-α inhibitor use. Being a pegylated humanised Fab monoclonal antibody, certolizumab pegol (CZP) is different from other TNF-α inhibitors. In clinical trials it has been shown to be just as, or even more, efficacious in the treatment of rheumatoid arthritis in combination with methotrexate compared with some of the earlier TNF-α inhibitors [1]. According to the US Food and Drug Administration and the European Medicines Agency, there have been no severe non-infectious adverse lung effects of CZP use. However, a systematic review of the literature revealed two previous cases of CZP-associated interstitial lung disease, one with fatal outcomes [2, 3]. This is a report of a patient with rheumatoid arthritis who developed severe acute pneumonitis after treatment with CZP. The patient is a 72-year-old female who had suffered from severe erosive seropositive (rheumatoid factor and …

Four cases of interstitial lung disease induced by erlotinib and a review of the literatures

厄洛替尼是一种口服表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKI），广泛应用于晚期非小细胞肺癌的治疗。尽管目前认为这类药物安全性良好，但可诱发严重的间质性肺病（interstitial lung disease, ILD）。文献中对吉非替尼所致ILD的报道较多，而对厄洛替尼所致的ILD报道较少。现报道上海市肺科医院4例厄洛替尼所致ILD，并复习相关文献，以使临床医生提高警惕。监测正在服用厄洛替尼患者的肺部症状、体征，做到及时诊断、尽早治疗对于厄洛替尼所致ILD的预后尤为重要。

A cohort study of mortality predictors and characteristics of patients with combined pulmonary fibrosis and emphysema

ObjectivesOur purpose was to assess the clinical data, predictors of mortality and acute exacerbation (AE) in combined pulmonary fibrosis and emphysema (CPFE) patients.DesignSingle-centre retrospective cohort study.SettingTeaching hospital in Japan.ParticipantsWe identified...

Fatal interstitial lung disease associated with high erlotinib and metabolite levels. A case report and a review of the literature

IntroductionErlotinib is an agent in the class of oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD). This potentially fatal adverse reaction has been often described with gefitinib, but has been less well described for erlotinib. We here describe a case report of fatal interstitial lung disease in a Caucasian man associated with erlotinib and high erlotinib and metabolite plasma levels and discuss it in the context of all documented cases of erlotinib associated ILD. MethodsOur case was described and for the literature review a Pubmed and Google Scholar search was conducted for cases of erlotinib associated ILD. The retrieved publications were screened for relevant literature. ResultsBesides our case, a total of 19 cases of erlotinib-associated ILD were found. Eleven out 19 cases had a fatal outcome and in only one case erlotinib plasma concentrations were measured and found to be high. ConclusionErlotinib-associated ILD is a rare, serious and often fatal adverse reaction. Most likely, the cause for erlotinib-associated ILD is multifactorial and high drug levels may be present in patients without serious adverse reactions. However, considering the pharmacology of EGFR inhibitors, high drug and metabolite levels may play a role and future studies are warranted to identify risk factors and to investigate the role of elevated levels of erlotinib and its metabolites in the development of pulmonary toxicity.

Elevation of Serum Thioredoxin in Patients with Gefitinib-induced Interstitial Lung Disease

Interstitial lung disease (ILD) is a severe adverse event of gefitinib therapy. However, the mechanism still remains unclear. The objective of this study was to examine whether or not oxidative stress, one of the common factors in drug-associated ILD, is involved in the pathogenesis of gefitinib-induced ILD. Using an enzyme-linked immunosorbent assay (ELISA), we measured the concentration of serum thioredoxin (Trx), a redox-active protein with antioxidative effects, in 44 patients treated with gefitinib, including three patients who had ILD. In patients who had gefitinib-induced ILD, serum Trx levels were significantly elevated. They decreased after cessation of gefitinib therapy accompanying clinical improvement of ILD. It was suggested that oxidative stress may be involved as a part of mechanisms causing or worsening gefitinib-induced ILD.

Les pneumopathies infiltrantes diffuses d’origine médicamenteuse : un problème avant tout diagnostique

Drugs are frequently incriminated as the cause of interstitial pneumonia. There are two major mechanisms of drug-associated interstitial lung disease: direct toxicity and immunoallergic reaction. When a drug is suspected, the difficulty lies in obtaining proof. The chronology of the disease and its manifestations together with earlier evidence reported in the literature can lead to a tentative diagnosis of drug-associated interstitial pneumonia. Proof is obtained through surveillance during the disease course. In nearly all patients, therapeutic decisions must be taken on the basis of suspected drug involvement.

Diagnosis and management of drug-associated interstitial lung disease.

Symptoms of drug-associated interstitial lung disease (ILD) are nonspecific and can be difficult to distinguish from a number of illnesses that commonly occur in patients with non-small-cell lung cancer (NSCLC) on therapy. Identification of drug involvement and differentiation from other illnesses is problematic, although radiological manifestations and clinical tests enable many of the alternative causes of symptoms in advanced NSCLC to be excluded. In lung cancer patients, high-resolution computed tomography (HRCT) is more sensitive than a chest radiograph in evaluating the severity and progression of parenchymal lung disease. Indeed, the use of HRCT imaging has led to the recognition of many distinct patterns of lung involvement and, along with clinical signs and symptoms, helps to predict both outcome and response to treatment. This manuscript outlines the radiology of drug-associated ILD and its differential diagnosis in NSCLC. An algorithm that uses clinical tests to exclude alternative diagnoses is also described.

Understanding the mechanisms of drug-associated interstitial lung disease.

Drugs have been implicated in lung injury as a result of direct pharmacological action, persistence or metabolism in the tissue, or via the production of a reactive metabolite or metabolites. The result of this apparent drug-associated injury ranges from cellular dysfunction through to cell death (apoptosis) and alteration of repair mechanisms that are essential in replacing critical tissue elements and function. There is limited knowledge on how timing of drug administration or drug interactions may interfere with the repair mechanisms or modulate the expression of pulmonary toxicity. Chemotherapeutic drugs and novel agents, such as those targeting the epidermal growth factor receptor (EGFR), appear to affect both normal and neoplastic cells. However, unlike chemotherapy, where the actions are systemic and directly as a result of biotransformation or cell injury, it has been postulated that effects of EGFR-targeting agents are more likely to be focused on epithelia via a pharmacological effect. Furthermore, risk factors for the development of adverse pulmonary reactions, as well as biological markers indicating incipient toxicity, need to be prospectively identified. Proteomics, through the identification of ⩾1000 proteins or peptides in blood samples, will hopefully identify candidates for this role.