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Thoracic Cancer Jan 2020The increasing use of immune checkpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by... (Review)
Review
The increasing use of immune checkpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immune checkpoint inhibitors, mainly activated T-cells, can attack normal tissues and organs in the body and lead to a variety of adverse effects. In the lung, these attacks can induce checkpoint inhibitor pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and has the potential to be fatal if not treated correctly. In this review, we summarize the characteristics of CIP and provide advice on how to manage this disease.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Neoplasms; Pneumonia; Prognosis
PubMed: 31762218
DOI: 10.1111/1759-7714.13240 -
Cancer Treatment Reviews May 2022Trastuzumab deruxtecan (T-DXd; DS-8201) is an antibody-drug conjugate targeting human epidermal growth factor receptor 2. Interstitial lung disease (ILD)/pneumonitis is... (Review)
Review
Multidisciplinary clinical guidance on trastuzumab deruxtecan (T-DXd)-related interstitial lung disease/pneumonitis-Focus on proactive monitoring, diagnosis, and management.
Trastuzumab deruxtecan (T-DXd; DS-8201) is an antibody-drug conjugate targeting human epidermal growth factor receptor 2. Interstitial lung disease (ILD)/pneumonitis is an adverse event associated with T-DXd; in most cases, it is low grade (grade ≤ 2) and can be treated effectively but may develop to be fatal in some instances. It is important to increase patient and provider understanding of T-DXd-related ILD/pneumonitis to improve patient outcomes. Drug-related ILD/pneumonitis is a diagnosis of exclusion; other possible causes of lung injury/imaging findings must be ruled out for an accurate diagnosis. Symptoms can be nonspecific, and identifying early symptoms is challenging; therefore, diagnosis is often delayed. We reviewed characteristics of patients who developed T-DXd-related ILD/pneumonitis and its patterns, produced multidisciplinary guidelines on diagnosis and management, and described areas for future investigation. Ongoing studies are collecting data on T-DXd-related ILD/pneumonitis to further our understanding of its clinical patterns and mechanisms. SEARCH STRATEGY AND SELECTION CRITERIA: References were identified based on the guidelines used by the authors in treating interstitial lung disease and pneumonitis. Searches of the authors' own files were also completed. A search of PubMed with the search terms (trastuzumab deruxtecan) AND (interstitial lung disease) AND (guidelines) was conducted on November 1, 2021, with no restrictions based on publication date, and the two articles yielded by the search were included.
Topics: Camptothecin; Humans; Immunoconjugates; Lung Diseases, Interstitial; Pneumonia; Trastuzumab
PubMed: 35430509
DOI: 10.1016/j.ctrv.2022.102378 -
Journal of Clinical Oncology : Official... Mar 2017Purpose Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs)....
Purpose Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Methods Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlying malignancy were examined with Fisher's exact test as were associations between pneumonitis features and outcomes. Results Of 915 patients who received anti-PD-1/PD-L1 mAbs, pneumonitis developed in 43 (5%; 95% CI, 3% to 6%; Memorial Sloan Kettering Cancer Center, 27 of 578 [5%]; Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%]; P < .01). Incidence was similar in patients with melanoma and non-small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%]; monotherapy, 15 of 417 v five of 152 [ P = 1.0]; combination, 11 of 115 v four of 57 [ P = .78]). Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. Conclusion Pneumonitis associated with anti-PD-1/PD-L1 mAbs is a toxicity of variable onset and clinical, radiologic, and pathologic appearances. It is more common when anti-PD-1/PD-L1 mAbs are combined with anti-cytotoxic T-cell lymphocyte-4 mAb. Most events are low grade and improve/resolve with drug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Humans; Immunotherapy; Membrane Transport Proteins; Middle Aged; Neoplasms; Pneumonia; Programmed Cell Death 1 Receptor; Treatment Outcome
PubMed: 27646942
DOI: 10.1200/JCO.2016.68.2005 -
Journal For Immunotherapy of Cancer Jan 2021Immune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression is termed... (Comparative Study)
Comparative Study
BACKGROUND
Immune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression is termed steroid-refractory ICI-pneumonitis. Herein, we report the clinical features, management and outcomes for patients treated with intravenous immunoglobulin (IVIG), infliximab, or the combination of IVIG and infliximab for steroid-refractory ICI-pneumonitis.
METHODS
Patients with steroid-refractory ICI-pneumonitis were identified between January 2011 and January 2020 at a tertiary academic center. ICI-pneumonitis was defined as clinical or radiographic lung inflammation without an alternative diagnosis, confirmed by a multidisciplinary team. Steroid-refractory ICI-pneumonitis was defined as lack of clinical improvement after high-dose corticosteroids for 48 hours, necessitating additional immunosuppression. Serial clinical, radiologic (CT imaging), and functional features (level-of-care, oxygen requirement) were collected preadditional and postadditional immunosuppression.
RESULTS
Of 65 patients with ICI-pneumonitis, 18.5% (12/65) had steroid-refractory ICI-pneumonitis. Mean age at diagnosis of ICI-pneumonitis was 66.8 years (range: 35-85), 50% patients were male, and the majority had lung carcinoma (75%). Steroid-refractory ICI-pneumonitis occurred after a mean of 5 ICI doses from PD-(L)1 start (range: 3-12 doses). The most common radiologic pattern was diffuse alveolar damage (DAD: 50%, 6/12). After corticosteroid failure, patients were treated with: IVIG (n=7), infliximab (n=2), or combination IVIG and infliximab (n=3); 11/12 (91.7%) required ICU-level care and 8/12 (75%) died of steroid-refractory ICI-pneumonitis or infectious complications (IVIG alone=3/7, 42.9%; infliximab alone=2/2, 100%; IVIG + infliximab=3/3, 100%). All five patients treated with infliximab (5/5; 100%) died from steroid-refractory ICI-pneumonitis or infectious complications. Mechanical ventilation was required in 53% of patients treated with infliximab alone, 80% of those treated with IVIG + infliximab, and 25.5% of those treated with IVIG alone.
CONCLUSIONS
Steroid-refractory ICI-pneumonitis constituted 18.5% of referrals for multidisciplinary irAE care. Steroid-refractory ICI-pnuemonitis occurred early in patients' treatment courses, and most commonly exhibited a DAD radiographic pattern. Patients treated with IVIG alone demonstrated an improvement in both level-of-care and oxygenation requirements and had fewer fatalities (43%) from steroid-refractory ICI-pneumonitis when compared to treatment with infliximab (100% mortality).
Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Drug Resistance; Female; Humans; Immune Checkpoint Inhibitors; Immunoglobulins, Intravenous; Incidence; Infliximab; Intensive Care Units; Lung Neoplasms; Male; Middle Aged; Pneumonia; Retrospective Studies; Survival Analysis
PubMed: 33414264
DOI: 10.1136/jitc-2020-001731 -
Infection Aug 2021Influenza virus, rhinovirus, and adenovirus frequently cause viral pneumonia, an important cause of morbidity and mortality especially in the extreme ages of life.... (Review)
Review
Influenza virus, rhinovirus, and adenovirus frequently cause viral pneumonia, an important cause of morbidity and mortality especially in the extreme ages of life. During the last two decades, three outbreaks of coronavirus-associated pneumonia, namely Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and the ongoing Coronavirus Infectious Disease-2019 (COVID-19) were reported. The rate of diagnosis of viral pneumonia is increasingly approaching 60% among children identified as having community-acquired pneumonia (CAP). Clinical presentation ranges from mild to severe pneumonitis complicated by respiratory failure in severe cases. The most vulnerable patients, the elderly and those living with cancer, report a relevant mortality rate. No clinical characteristics can be useful to conclusively distinguish the different etiology of viral pneumonia. However, accessory symptoms, such as anosmia or ageusia together with respiratory symptoms suggest COVID-19. An etiologic-based treatment of viral pneumonia is possible in a small percentage of cases only. Neuraminidase inhibitors have been proven to reduce the need for ventilatory support and mortality rate while only a few data support the large-scale use of other antivirals. A low-middle dose of dexamethasone and heparin seems to be effective in COVID-19 patients, but data regarding their possible efficacy in viral pneumonia caused by other viruses are conflicting. In conclusion, viral pneumonia is a relevant cause of CAP, whose interest is increasing due to the current COVID-19 outbreak. To set up a therapeutic approach is difficult because of the low number of active molecules and the conflicting data bearing supportive treatments such as steroids.
Topics: Age Factors; COVID-19; Humans; Pneumonia, Viral
PubMed: 33782861
DOI: 10.1007/s15010-021-01603-y -
Physiological Research Dec 2021Aspiration is a common condition affecting healthy or sick patients which could create an acute or chronic inflammatory reaction in the lungs. Aspiration syndromes could... (Review)
Review
Aspiration is a common condition affecting healthy or sick patients which could create an acute or chronic inflammatory reaction in the lungs. Aspiration syndromes could be categorized according to a content entering the respiratory system into bacterial aspiration pneumonia with the gastric or oropharyngeal bacteria entering, aspiration chemical pneumonitis with bacteria-freegastric acid aspiration, or aspiration of a foreign body which causes an acute pulmonary emergency. There are differences in the clinical presentation of volume-dependent aspirations (microaspiration and macroaspiration): the higher is the volume of aspiration, the greater is the injury to the patient and more serious are the health consequences (with 70 % mortality rate for hospitalized patients). Aspiration syndromes can affect both the airways and pulmonary parenchyma, leading to acute lung injury, increased hospitalization rate and worse outcomes in critically ill patients. Impaired alveolar-capillary permeability, oedema formation, neutrophilic inflammatory response and pulmonary surfactant inactivation lead to reduced lung compliance and loss of aerated lung tissue and give rise to hypoxemia and respiratory failure. This review discusses the effect of aspiration events on the pulmonary tissue. The main focus is to distinguish the differences between bacterial and chemical pneumonia, their clinical presentation and symptoms, risk factors of developing the changes, possibilities of diagnostics and management as well as prevention of aspirations. Because of a risk of serious lung damage after the aspiration, pathophysiology and processes leading to lung tissue injury are discussed in detail. Data sources represent a systematic literature search using relevant medical subject headings.
Topics: Acute Lung Injury; Humans; Incidence; Lung; Pneumonia, Aspiration; Syndrome
PubMed: 35199544
DOI: 10.33549/physiolres.934767 -
Chest Dec 2018Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that have been shown to improve survival in advanced non-small cell lung cancer (NSCLC). Unlike... (Review)
Review
Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that have been shown to improve survival in advanced non-small cell lung cancer (NSCLC). Unlike traditional chemotherapeutic agents, ICIs work by boosting the body's natural tumor killing response. However, this unique mechanism of action has also led to the recognition of class-specific side effects. Labeled immune-related adverse events, these toxicities can affect multiple organ systems including the lungs. Immune-mediated lung injury because of ICI use, termed checkpoint inhibitor pneumonitis (CIP), occurs in about 3% to 5% of patients receiving ICIs; however, the real-world incidence of this entity may be higher, especially now that ICIs are being used in nonclinical trial settings. In this review, we briefly introduce the biology of ICIs and the indications for ICI use in NSCLC and then discuss the epidemiology and clinical and radiologic manifestations of CIP. Next, we discuss management strategies for CIP, including the current consensus on management of steroid-refractory CIP. Given the nascent nature of this field, we highlight areas of uncertainty and emerging research questions in the burgeoning field of checkpoint inhibitor pulmonary toxicity.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Immunotherapy; Lung Neoplasms; Patient Care Management; Pneumonia; Risk Adjustment
PubMed: 30189190
DOI: 10.1016/j.chest.2018.08.1048 -
Frontiers in Immunology 2022Immune checkpointty inhibitors (ICIs), particularly those targeting programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1), enhance the antitumor effect by... (Review)
Review
Immune checkpointty inhibitors (ICIs), particularly those targeting programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1), enhance the antitumor effect by restoring the function of the inhibited effector T cells and produce durable responses in a large variety of metastatic and late patients with non-small-cell lung cancer. Although often well tolerated, the activation of the immune system results in side effects known as immune-related adverse events (irAEs), which can affect multiple organ systems, including the lungs. The occurrence of severe pulmonary irAEs, especially checkpoint inhibitor pneumonitis (CIP), is rare but has extremely high mortality and often overlaps with the respiratory symptoms and imaging of primary tumors. The development of CIP may be accompanied by radiation pneumonia and infectious pneumonia, leading to the simultaneous occurrence of a mixture of several types of inflammation in the lungs. However, there is a lack of authoritative diagnosis, grading criteria and clarified mechanisms of CIP. In this article, we review the incidence and median time to onset of CIP in patients with non-small-cell lung cancer treated with PD-1/PD-L1 blockade in clinical studies. We also summarize the clinical features, potential mechanisms, management and predictive biomarkers of CIP caused by PD-1/PD-L1 blockade in non-small-cell lung cancer treatment.
Topics: B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Programmed Cell Death 1 Receptor
PubMed: 35464480
DOI: 10.3389/fimmu.2022.830631 -
Advances in Experimental Medicine and... 2020Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major... (Review)
Review
Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major challenge in the treatment of cancer patients. Pneumonitis is a rare immune-related adverse event that presents in distinct patterns. The goal of this chapter is to instruct readers on the incidence and clinical manifestations of pneumonitis and to offer guidance in the evaluation and treatment of patients with pneumonitis.
Topics: Humans; Immunotherapy; Incidence; Neoplasms; Pneumonia
PubMed: 32301020
DOI: 10.1007/978-3-030-41008-7_13 -
Tuberkuloz Ve Toraks Mar 2023Hypersensitivity pneumonitis (HP) is an immunological lung disease that affects individuals who are sensitive and susceptible to occupational and environmental... (Review)
Review
Hypersensitivity pneumonitis (HP) is an immunological lung disease that affects individuals who are sensitive and susceptible to occupational and environmental exposures. While clinical and radiological findings may resemble other interstitial lung diseases, identifying the causative agents can aid in the differential diagnosis. However, this can be challenging and may result in delayed diagnosis and poor prognosis. A gold standard test for diagnosis is currently unavailable, and therefore, a multidisciplinary approach involving a clinician, radiologist, and pathologist is necessary. Avoiding exposure is the first step in treatment, with immunosuppressive therapeutics also being used. Antifibrotic agents show promise for future treatment approaches. Despite recent advancements in data and guidelines, knowledge about managing occupational HP remains limited. This review provides a summary of the epidemiological, clinical, and radiological findings, as well as diagnostic and treatment principles of occupational HP based on current literature.
Topics: Humans; Alveolitis, Extrinsic Allergic; Lung; Lung Diseases, Interstitial; Environmental Exposure; Pneumonia
PubMed: 36912413
DOI: 10.5578/tt.20239911