Drug-induced Interstitial Lung Disease Research Articles

EP14.05-022 The Drug Induced Interstitial Lung Disease in Chemoimmunotherapy for Extensive-Stage Small Cell Lung Cancer

Interstitial lung abnormalities (ILA) is defined as the changes affecting more than 5% of any lung zone, which included ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis. ILA has been reported to be a risk factor for the development of drug-induced interstitial lung disease (D-ILD) by immune checkpoint inhibitors (ICI) monotherapy in non-small cell lung cancer. Combination of chemotherapy and immunotherapy (Chemo-ICI) has become the new standard of treatment for extensive-stage small cell lung cancer (ES-SCLC).

Efficacy of lorlatinib after alectinib-induced interstitial lung disease in a patient with anaplastic lymphoma kinase-positive non-small cell lung cancer: a case report

BackgroundAnaplastic lymphoma kinase tyrosine kinase inhibitors are standard therapeutic agents prescribed for anaplastic lymphoma kinase-positive non-small cell lung cancer, and treatment with these agents has been shown to contribute to long-term survival in patients. However, there is no consensus regarding the course of treatment after the onset of anaplastic lymphoma kinase tyrosine kinase inhibitors related drug-induced interstitial lung disease.Here, we present a case of successful lorlatinib treatment after the onset of drug-induced interstitial lung disease caused by alectinib.Case presentationA 57-year-old Japanese man was diagnosed with stage IVB non-small cell lung cancer by bronchoscopy, but gene mutation testing could not be performed because of the small amount of specimen. After diagnosis, first-line therapy with cisplatin/pemetrexed was initiated, but the patient developed renal dysfunction. Bronchoscopy was performed again to guide further treatment, and the non-small cell lung cancer was found to be anaplastic lymphoma kinase positive. Alectinib was started after the onset of progressive disease, but it resulted in drug-induced interstitial lung disease, necessitating alternative treatments. He subsequently received nanoparticle albumin bound paclitaxel, which was halted in view of the renal dysfunction. Thereafter, lorlatinib was administered, which was continued without drug-induced interstitial lung disease relapse.ConclusionSince alectinib can occasionally cause drug-induced interstitial lung disease, as in the present case, lorlatinib may be an option to continue treatment in patients without other treatment alternatives.

Expert consensus on the diagnosis and treatment of anticancer drug-induced interstitial lung disease

Drug-induced interstitial lung disease (DILD) is the most common pulmonary adverse events caused by anti-cancer treatment. In recent years, with the development of clinical oncology, a large amount of novel anti-cancer drugs have been approved and widely used in clinical practice, and the incidence of anti-cancer drug related DILD is gradually increasing. DILD lacks specific clinical manifestations or diagnostic criteria. If not treated properly, it may leads to interruption or discontinuation of anti-cancer treatment, or even become life threat in severe cases. Therefore, the Anti-cancer Drug-induced Interstitial Lung Disease Management Group have reached a consensus on the diagnosis and management of anti-cancer DILD after several rounds of discussion. This consensus aims to improve clinicians' awareness of anti-cancer drug related-DILD and proposes an algorithm for the diagnosis and treatment of this disease, and to improve patients' prognosis and quality of life.

Stelara struck: a case of noninfectious pneumonitis secondary to ustekinumab

BackgroundWe describe a case of acute hypoxic respiratory failure due to drug induced lung disease secondary to ustekinumab, which is a monoclonal antibody used to treat psoriasis, psoriatic arthritis, and inflammatory bowel disease.Case presentationA 33-year-old man with a history of Crohn’s disease presented with fevers, myalgias, and abdominal pain, and subsequently developed acute hypoxemic respiratory failure approximately 2 weeks after restarting ustekinumab for his Crohn’s disease. Cross-sectional chest imaging showed ground glass opacities and bilateral consolidations. Due to progressive hypoxia, he ultimately required intubation and mechanical ventilation. Broad infectious and autoimmune work up was negative, making drug induced interstitial lung disease (DILD) the leading consideration. He was treated with high dose steroids with dramatic improvement in his respiratory status. At follow up, his imaging findings had largely resolved, and his pulmonary function tests were normal.ConclusionsFor patients presenting with acute hypoxic respiratory failure, it is critical to identify the underlying cause. In addition to testing for common respiratory infections that can cause respiratory failure, patients should also be evaluated for risk factors for developing atypical or opportunistic infections as well as inflammatory pneumonitis. Due to receiving ustekinumab, our patient was both at risk for developing an opportunistic infection as well as DILD. Although rare, DILD is a recognized toxicity of ustekinumab. Ustekinumab can cause significant lung injury, as in our patient, but with steroids and avoidance of future doses of the medication, our patient demonstrated good recovery. Reassuring outcomes have similarly been described in the literature; however, this case provides further details about outcomes with long-term follow-up clinical, imaging, and pulmonary function testing data available. We recommend consideration of high dose steroids for these patients for whom DILD is suspected.

V. Drug-induced Interstitial Lung Disease

V. Drug-induced Interstitial Lung Disease

Awareness towards the main ILD among primary care physicians

BackgroundInterstitial lung diseases (ILDs) comprise a group of multiple entities sharing some clinical, functional, and radiological similarities. In many countries primary care setting has been devoid of pre- and post-graduate educational interventions focused on basic knowledge on ILD. This, along with usual nonspecificity of symptoms at presentation, may contribute to diagnostic delay in this disease setting.MethodsWe designed a study questionnaire to assess the level of awareness on basic diagnostic and management aspects of core ILDs – idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, sarcoidosis, connective tissue disease related-ILD, and drug-induced ILD - among primary care physicians (GPs) from five “ACeS Baixo Vouga” health centres and to perceive possible weaknesses. Differences in awareness between GPs under 45 and over 45 yearsold were also assessed.ResultsGlobally, 69% of questions were correctly answered but only 21.9% of GPs considered to have a satisfactory self-perceived level of knowledge on ILD. Except sarcoidosis (p=0.017) and some isolated questions on other diseases, no significant differences were found between physicians below 45 years and above. Though, there was a trend to higher awareness in the younger group. The best awareness was seen in sarcoidosis. IPF questions had the worst performance and only 48.5% of GPs recognized the importance of velcro-type crackles in suggesting a possible diagnosis.ConclusionSpecific attention should be devoted to educational interventions directed to GPs on basic notions on the main ILDs. This could improve the usual diagnostic delay in many ILDs, as a timely diagnosis is essential for an early treatment and prolonged patient survival.

Drug-induced interstitial lung disease.

Interstitial lung disease (ILD) secondary to drug-induced lung injury is an increasingly common cause of morbidity and mortality. The number of drugs associated with the development of ILD continues to rise, mainly due to the use of novel monoclonal antibodies and biologicals for neoplastic and rheumatological diseases, and includes, among others, chemotherapeutics, molecular targeting agents, immune checkpoint inhibitors, antibiotics, antiarrhythmics and conventional or biological disease-modifying antirheumatic drugs. Drug-induced ILD (DI-ILD) manifests with a variety of clinical patterns, ranging from mild respiratory symptoms to rapidly progressive respiratory failure and death. In most cases, there are no pathognomonic clinical, laboratory, radiological or pathological features and the diagnosis of DI-ILD is suspected in the presence of exposure to a drug known to cause lung toxicity and after exclusion of alternative causes of ILD. Early identification and permanent discontinuation of the culprit drug are the cornerstones of treatment with systemic glucocorticoids being used in patients with disabling or progressive disease. However, for certain drugs, such as checkpoint inhibitors, the frequency of lung toxicity is such that mitigation strategies are put in place to prevent this complication, and occurrence of DI-ILD is not necessarily synonymous with permanent drug discontinuation, particularly in the absence of valid therapeutic alternatives.

Incidence and prognostic factors in severe drug-induced interstitial lung disease caused by antineoplastic drug therapy in the real world

PurposeInvestigate the frequency and prognostic factors of severe drug-induced interstitial lung disease (DILD) caused by antineoplastic drugs regardless of cancer types or type of drugs.MethodsFrom 2014 to 2018, we reviewed patients with a history of antineoplastic agents administration in the real-world database of our hospital's electronic medical record and extracted patients who experienced "severe" DILD, requiring hospitalization with treatment or developed during hospitalization and required treatment. We collected patients' backgrounds, clinical and radiological features, laboratory data, treatment, and survival outcomes.Results19,132 cancer patients received antineoplastic drug therapy during the study period, and 120 (0.62%) experienced severe DILD. The incidence of severe DILD in patients with thoracic cancer was highest among the patients included in this analysis (2.52% vs. 0.34% other cancers). Diffuse alveolar damage (DAD) pattern on CT was associated with higher mortality in patients with severe DILD compared with non-DAD pattern (hazard ratio [HR], 11.24; 95% CI, 4.82–26.2). Multivariate analysis revealed that the DAD pattern at diagnosis as severe DILD (HR, 3.59; 95% CI, 1.17–11.03), concurrent/previous interstitial lung disease (HR, 3.20; 95% CI, 1.27–8.10), and ECOG performance status of 2–4 (HR, 3.81; 95% CI, 1.10–13.17) were independent risk factors for mortality in patients with severe DILD.ConclusionsThe frequency of severe DILD was highest in patients with thoracic cancer. The DAD pattern was associated with a poor outcome. From the perspective of DILD, special attention should be paid when administering antineoplastic agents to patients with thoracic cancer.

Editorial introductions

Current Opinion in Pulmonary Medicine was launched in 1995. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of pulmonary medicine is divided into nine sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Editors in Chief and Section Editors for this issue. EDITORS IN CHIEF Robert BaughmanRobert BaughmanDr Robert Baughman is Professor of Medicine at the University of Cincinnati, USA. After completing undergraduate training at Yale University, USA, he received his medical degree from Case Western Reserve School of Medicine, USA. He joined the Internal Medicine staff at the University of Cincinnati after completing both an internal medicine residency and fellowship training in pulmonary diseases at the University of Cincinnati. His major research interests include the treatment of sarcoidosis and bronchoalveolar lavage. Along with his long-time collaborator Dr Elyse Lower, he has developed several novel treatments for sarcoidosis, including methotrexate, thalidomide, leflunomide, and infliximab. Current studies include treatments for sarcoidosis associated fatigue and pulmonary hypertension due to sarcoidosis. Dr Baughman's publications include over 200 original papers and over 70 review articles and/or book chapters. He is on the editorial board of several journals and co-Editor of the journals Current Opinion in Pulmonary Medicine and Sarcoidosis, Interstitial Lung Disease, and Vasculitis. In addition, Dr Baughman is the editor of books on sarcoidosis, interstitial lung disease, and interstitial lung disease associated pulmonary hypertension. Marjolein DrentMarjolein DrentDr Marjolein Drent is Professor of Interstitial Lung Diseases (ILD) at the Department of Pharmacology and Toxicology of the Faculty of Heath, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands, and Pulmonologist at the ILD Center of Excellence St. Antonius Hospital, Nieuwegein, Netherlands. Her oration was entitled: ‘Breathtaking inspirations’. After she finished her training as a physical therapist, she received her medical degree from the Catholic University of Nijmegen, Netherlands. Her major research interests include sarcoidosis, ILD, drug-induced ILD and quality of life related topics. She is a co-editor, member of the editorial board and guest editor of several international journals, as well as editor of ILD Care Today. She has (co-) authored over 400 papers and book chapters. She is the co-editor of several ILD related e-learning modules. She is president emeritus of WASOG (World Association of Sarcoidosis and other Granulomatous diseases). She is a member of the Foundation for Sarcoidosis Research (FSR) Scientific Advisory Board. She is the founder and chair of the ILD Care (interstitial lung diseases including sarcoidosis and lung diseases related to occupation and environment management and research) Foundation. She is an honorary member of Sarcoidose.nl (Dutch Sarcoidosis Society) and co-founder and a member of the advisory board of the Dutch Pulmonary Fibrosis Society. In 2012, she was nominated for the World Sarcoidosis Person of the Year Award for her tireless research work in defining the psychological burden faced by patients and their families. Dublin, Ireland. She is ambassador for Compassion for Care and the youth smoking prevention foundation. She was appointed as an Officer in the Order of Orange Nassau by Royal Decree. This royal honour was awarded in 2016 by the deputy mayor of Ede, Netherlands. SECTION EDITORS Sadia BenzaquenSadia BenzaquenSadia Benzaquen, MD, FACP, FCCP, ATSF, DAABIP is the Chairman of Pulmonary, Critical Care, Sleep and Allergy at Einstein Medical Center, Philadelphia, USA. He is a Professor of Medicine at the Sidney Kimmel Medical College at Jefferson University, Philadelphia, USA. He is an expert in the interventional pulmonology field with extensive research and publications in lung cancer, pleural disease and ILD. Sara TomassettiSara TomassettiSara Tomassetti is currently Associate Professor of Respiratory Medicine at Florence University, Italy, and Head of Interventional Pulmonology Unit at Careggi University Hospital, Florence, Italy. She has extensive experience in all aspects of interstitial lung diaseses and interventional pulmonology, including cryobiopsy. She is a faculty member of the European Respiratory Society, and BOND National member for Italy of the European Association for Bronchology and Interventional Pulmonology. From a clinical research perspective, she has been the primary investigator (PI) of several sponsored and investigator initiated clinical trials on diagnosis and treatemnt of ineterstiatial lung diseases and idiopathic pulmonary fibrosis. She publishes on clinical research aspects of interstitial lung diseases and interventional pulmonology. She regularly reviews research and clinical manuscripts for international journals.

Animal models of drug-induced pulmonary fibrosis: an overview of molecular mechanisms and characteristics.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by progressive loss of pulmonary function. Drug-induced interstitial lung disease has been reported as a severe adverse effect of some drugs, such as bleomycin, amiodarone, and methotrexate. Based on good characteristics, drug-induced pulmonary fibrosis (PF) animal model has played a key role in our understanding of the molecular mechanisms of PF pathogenesis and recapitulates the specific pathology in patients and helps develop therapeutic strategies. Here, we summarize the mechanisms and characteristics of given fibrotic drug-induced animal models for PFs. Together with the key publications describing these models, this brief but detailed overview would be helpful for the pharmacological research with animal models of PFs. Potential mechanisms underlying drug induced lung toxicity.

Role of Drug-Gene Interactions and Pharmacogenetics in Simvastatin-Associated Pulmonary Toxicity.

IntroductionSimvastatin has previously been associated with drug-induced interstitial lung disease. In this retrospective observational study, cases with non-specific interstitial pneumonia (NSIP) or idiopathic pulmonary fibrosis (IPF) with simvastatin-associated pulmonary toxicity (n = 34) were evaluated.ObjectiveTo identify whether variations in genes encoding cytochrome P450 (CYP) enzymes or in the SLCO1B1 gene (Solute Carrier Organic anion transporting polypeptide 1B1 gene, encoding the organic anion transporting polypeptide 1B1 [OATP1B1] drug transporter enzyme), and/or characteristics of concomitantly used drugs, predispose patients to simvastatin-associated pulmonary toxicity.MethodsCharacteristics of concomitantly used drugs and/or variations in the CYP or SLCO1B1 genes and drug–gene interactions were assessed. The outcome after withdrawal of simvastatin and/or switch to another statin was assessed after 6 months.ResultsMultiple drug use involving either substrates and/or inhibitors of CYP3A4 and/or three or more drugs with the potential to cause acidosis explained the simvastatin-associated toxicity in 70.5% (n = 24) of cases. Cases did not differ significantly from controls regarding CYP3A4, CYP2C9, or OATP1B1 phenotypes, and genetic variation explained only 20.6% (n = 7) of cases. Withdrawal of simvastatin without switching to another statin or with a switch to a hydrophilic statin led to improvement or stabilization in all NSIP cases, whereas all cases who were switched to the lipophilic atorvastatin progressed.ConclusionSimvastatin-associated pulmonary toxicity is multifactorial. For patients with this drug-induced pulmonary toxicity who need to continue taking a statin, switching to a hydrophilic statin should be considered.ClinicalTrials.gov identifierNCT00267800, registered in 2005.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01105-8.

SNAP, CRACKLE, AND POP: A CASE OF PEMETREXED-INDUCED INTERSTITIAL PNEUMONITIS

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pemetrexed is a folic acid inhibitor which is used for the treatment of non-small cell lung cancer (NSCLC) (1). Pemetrexed is generally well tolerated, but interstitial pneumonitis is an exceedingly rare, potentially fatal adverse effect (2). The diagnosis of drug induced interstitial pneumonitis is one of exclusion and based on nonspecific clinical and radiographic findings. Onset of symptoms must correlate clinically with timing of administration of the offending agent, and the symptoms improve with removal of the medication and initiation of corticosteroids (3). It is important for clinicians to have a high index of suspicion to initiate early treatment, reducing morbidity and mortality. Below is a case of a patient with lung adenocarcinoma who developed pemetrexed induced interstitial pneumonitis. CASE PRESENTATION: Our patient is an 85 year old man who was diagnosed with stage IVA lung adenocarcinoma. He received two cycles of Carboplatin and Pemetrexed with good radiologic response but experienced intolerable side effects. The decision was made to transition to Pemetrexed monotherapy. Two weeks after his second cycle, he developed dyspnea, low grade fevers and fatigue, requiring supplemental oxygen (Vapotherm 60% FiO2 at 40 L/min) and hospital admission. Physical exam was notable for diffuse crackles bilaterally. CTA Chest demonstrated bilateral ground glass opacities and was negative for pulmonary embolism. He was empirically started on broad spectrum antibiotics for multifocal pneumonia. COVID-19, respiratory viral test, blood and sputum cultures were all negative. Bronchoscopy with bronchoalveolar lavage (BAL) demonstrated normal airways. There was no evidence of alveolar hemorrhage. BAL cell count and differential was notable for a lymphocytic predominance. BAL cytology demonstrated pulmonary macrophages and mixed inflammatory cells but no atypical cells. High dose corticosteroids were started on hospital day five. Oxygen requirement steadily decreased, and he was discharged a few days later on 2 L NC and a prolonged corticosteroid taper. DISCUSSION: Pemetrexed is a widely used first-line treatment for NSCLC. Pemetrexed-induced interstitial pneumonitis has a range of clinical presentations, making it challenging to diagnose. Presentations vary from asymptomatic to life-threatening requiring mechanical ventilation. Moreover, it is a very rare side effect of Pemetrexed. This case highlights the importance of having strong clinical suspicion so that interstitial pneumonitis can be identified and treated early, mitigating morbidity and mortality. A thorough workup must be completed to rule out other causes, especially infection. CONCLUSIONS: Through early diagnosis, pemetrexed can be discontinued and corticosteroids can be initiated sooner, reducing risk to the patient and improving clinical outcomes (3). The patient should not be rechallenged with Pemetrexed, as this could be fatal. REFERENCE #1: Dhakal, B., Singh, V., Shrestha, A., Rao, A., & Choong, N. (2011). Pemetrexed induced pneumonitis. Clinics and Practice 1(4), 232-6. DOI: 10.4081/cp.2011.e106 REFERENCE #2: Kim, KH. et al. (2013). Interstitial pneumonitis after treatment with pemetrexed for non-small cell lung cancer. Cancer Research and Treatment 45(1), 74-7. DOI: 10.4143/crt.2013.45.1.74 REFERENCE #3: Skeoch, S. et al. (2018). Drug-induced interstitial lung disease: A systematic review. Journal of Clinical Medicine 7(10), 1-30. DOI: 10.3390/jcm7100356 DISCLOSURES: No relevant relationships by Brent Bagley, source=Web Response No relevant relationships by Ethan Tope, source=Web Response

A RARE CAUSE OF INTERSTITIAL LUNG DISEASE

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Clinicians should be aware of the potential adverse effects and complications that can occur with molecularly targeted agents for them to be able to diagnose and treat the condition. CASE PRESENTATION: 65-year-old female with stage IV epidermal growth factor receptor (EGFR) lung adenocarcinoma with metastases to the brain, spine, liver, and kidneys undergoing treatment with osimertinib for two months presented with a subjective fever of 102 °F. On admission the patient was tachycardic with an elevated lactate warranting investigation and treatment of sepsis secondary to a UTI. Despite using broad spectrum antibiotics and proper fluid resuscitation, her hospital course was complicated with the development of a new onset dyspnea with exertion and insidious hypoxic respiratory failure. Computed tomography angiography (CTA) of the chest revealed an incidental sub segmental pulmonary embolism which was not treated with anticoagulation due to underlying hemorrhagic brain metastasis. More importantly, the CTA showed new ground glass opacities demonstrated on the upper lung fields concerning for interstitial lung disease (ILD). Osimertinib was discontinued and high-dose IV methylprednisolone was administered resulting in immediate relief of dyspnea and cessation of relapsing fever. There was also a significant improvement to the hypoxia within a 24-hour period. Patient was transitioned to oral prednisone and discharged home the following day. DISCUSSION: Anti-epidermal growth factor receptor agents, a class of small molecule kinase inhibitors, are primarily used for the treatment of advanced non-small cell lung cancer. Common side effects for this particular class of tyrosine kinase inhibitors (TKIs) include fatigue, rashes, and lymphopenia. The risk of ILD for patient's taking EGFR-TKIs is a rare incidence, occurring at a rate of 1-3%, within the first 2-3 months of initiating therapy. The exact mechanism of TKI induced lung injury remains unknown, the proposing theory is an interruption to the alveolar repair mechanism which potentiates lung injury to other causes, such as sepsis, medications, and prior radiation therapy. Discontinuation of EGFR-TKIs therapy is the primary modality to prevent worsening of ILD. Utilization of high-dose glucocorticoids is an additional measure that can be employed for the treatment of drug-induced ILD. CONCLUSIONS: Physicians must be vigilant, with a high degree of clinical suspicion, to discontinue the offending agent in the event that a patient on EGFR-TKIs therapy presents with fever, acute dyspnea with or without cough, tachycardia, and hypoxia. If symptoms of the adverse reaction are not recognized early enough, they may progress to other conditions, such as pulmonary fibrosis. In addition, there is an increased mortality ratewith the continuation of these agents once ILD develops. REFERENCE #1: Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib.Ann Oncol. 2019;30(5):839. DISCLOSURES: No relevant relationships by Ankita Aggarwal, source=Web Response No relevant relationships by Yashar Eshman, source=Web Response no disclosure on file for Mohammad Fityan; No relevant relationships by Victoria Gonzalez, source=Web Response No relevant relationships by Zain Kulairi, source=Web Response

Drug Repurposing Prediction and Validation From Clinical Big Data for the Effective Treatment of Interstitial Lung Disease.

Interstitial lung diseases (ILDs) are a group of respiratory disorders characterized by chronic inflammation and fibrosis of the pulmonary interstitial tissues. Although the etiology of ILD remains unclear, some drug treatments are among the primary causes of ILD. In the present study, we analyzed the FDA Adverse Event Reporting System and JMDC Inc. insurance claims to identify a coexisting drug that reduced the incidence of ILD associated with the use of an anti-arrhythmic agent, amiodarone, and found that the thrombin inhibitor dabigatran prevented the amiodarone-induced ILD in both clinical datasets. In an experimental validation of the hypothesis, long-term oral treatment of mice with amiodarone caused a gradual decrease in body weight caused by respiratory insufficiency. In the lungs of amiodarone-treated mice, infiltration of macrophages was observed in parallel with a delayed upregulation of the platelet-derived growth factor receptor α gene. In contrast, co-treatment with dabigatran significantly attenuated these amiodarone-induced changes indicative of ILD. These results suggest that dabigatran is effective in preventing drug-induced ILD. This combinatorial approach of drug repurposing based on clinical big data will pave the way for finding a new treatment with high clinical predictability and a well-defined molecular mechanism.

Drugs associated with drug-induced interstitial lung diseases

Interstitial lesion is one of the causes of respiratory failure. Drugs are a modifiable etiological factor of lung damage. Medications most commonly associated with drug-induced interstitial lung disease include antineoplastic drugs, disease-modifying anti-rheumatic drugs and amiodarone. According to the latest literature data, the previously described link between anti-rheumatic drugs and interstitial lung diseases is very inconsistent. It may even be a protective effect of this group of drugs on the lung tissue. The relationship between statin use and interstitial lesions is also complex and not fully understood. It is necessary to carefully assess the appearance of respiratory tract complaints in patients taking statins as in other groups of patients. Prescription of additional diagnostic methods is necessary to close monitoring and prevention the toxic effect of these drugs. These actions, as well as the potential prescription of steroid therapy and change in the underlying disease treatment approaches, are an important factor in reducing the incidence of respiratory failure in the population.

Commentary: Imaging Biomarkers and Pathobiological Profiling in a Rat Model of Drug-Induced Interstitial Lung Disease (DIILD) Induced by Bleomycin.

Commentary: Imaging Biomarkers and Pathobiological Profiling in a Rat Model of Drug-Induced Interstitial Lung Disease (DIILD) Induced by Bleomycin.

An update on interstitial lung disease.

Interstitial lung diseases are a complex group of conditions that cause inflammation and scarring of the lung interstitium. This article discusses the diagnosis and management of common interstitial lung diseases including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, connective tissue disease associated-interstitial lung disease, sarcoidosis and drug-induced interstitial lung disease. A multidisciplinary approach to diagnosis of interstitial lung disease is the gold standard; key history and examination features, blood panel, pulmonary function tests, high resolution computed tomography imaging, and when required bronchoalveolar lavage and lung biopsy results are discussed to reach a multidisciplinary consensus diagnosis. Advances, including the development of the disease-modifying anti-fibrotic medications nintedanib and pirfenidone, continue to shape the future management of interstitial lung disease. A holistic approach to the care of patients with interstitial lung disease is paramount, as they often have a high symptom burden and considerable palliative care needs.

Prognosis of Patients With Interstitial Lung Disease Induced by Different Pharmacological Types of Anticancer Drugs.

The aim of this study was to evaluate the effect of drug-induced interstitial lung disease (DILD) on treatment outcomes by comparing the mortality of patients with DILD induced by different pharmacological types of anticancer drugs. Japanese patients with lung cancer who had received chemotherapy at Fujita Health University Hospital were enrolled. The primary outcome was the short-term mortality rate from the administration of chemotherapy that might have caused DILD. Eleven, 16, and 20 patients with DILD were assigned to the kinase inhibitor (KI), immune-checkpoint inhibitor (ICI), and cytotoxic anticancer drug groups, respectively. The 90-day mortality rate after the DILD event in the group treated with cytotoxic anticancer drugs was significantly higher than in the KI and ICI groups. Patients with DILD induced by cytotoxic anticancer drugs have poorer prognoses than those with DILD induced by KIs or ICIs.

Risk of drug-induced interstitial lung disease in hospitalised patients: a nested case–control study

IntroductionInformation on drug-induced interstitial lung disease (DILD) is limited due to its low incidence. This study investigated the frequencies of drug categories with potential risk in patients developing DILD during...

Diagnosis and treatment of drug-induced interstitial lung disease

Drug-induced interstitial lung disease (DILD) is a group of adverse drug reactions that is rare but fatally toxic. Pulmonary toxicity causes inflammation and subsequent interstitial fibrosis. As novel drugs with a variety of purposes are introduced into the medical field, the number of culprit medications that are suspected to cause lung complications is accordingly increasing. In this review, DILD will be discussed from several aspects such as causality by numerous drugs, check points for a timely diagnosis, alongside some contemporary treatment options. The exact mechanism of DILD has not been elucidated, and a useful clinical, radiological, or pathological confirmation process is still lacking. Common drugs which casue DILD include bleomycin, amiodarone, epidermal growth factor receptor-targeted agents, and immune checkpoint inhibitors. Diagnosis is based on a suspicious drug administration history, somewhat inconsistent clinical symptoms and signs, radiological hints, and histopathological assistance, together with the exclusion of other lung-injuring etiologies. Cessation of the suspected drug, meticulous corticosteroid usage, and ancillary supportive management are the mainstay therapeutic strategy for DILD. Most cases of DILD respond to these countermeasures and reductions, but in some cases the fibrotic process worsens, leading to irreversible sequelae on the affected lung.