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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 Nov 2022Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung...
Drug-Related Pneumonitis Induced by Osimertinib as First-Line Treatment for Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Real-World Setting.
BACKGROUND
Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data currently are lacking.
RESEARCH QUESTION
What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP?
STUDY DESIGN AND METHODS
We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest CT scans and clinical information during osimertinib exposure were collected until June 2020. The primary end point was DRP incidence identified through central review.
RESULTS
A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) had a diagnosis of DRP (all grades), and 21 patients (4.6%) had a diagnosis of grade 3 or more DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT scan patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and nonspecific interstitial pneumonia were found in 30, 21, 18, 9, and two patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio, 1.72; 95% CI, 1.01-2.89; P = .046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not affect treatment efficacy negatively.
INTERPRETATION
For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Cohort Studies; ErbB Receptors; Mutation; Pneumonia; Protein Kinase Inhibitors
PubMed: 35661746
DOI: 10.1016/j.chest.2022.05.035 -
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 -
Respiratory Investigation Jan 2022In the 21st century, aspiration pneumonia (ASP) is very common in older patients, and has a high mortality rate. ASP is diagnosed following confirmation of inflammatory... (Review)
Review
In the 21st century, aspiration pneumonia (ASP) is very common in older patients, and has a high mortality rate. ASP is diagnosed following confirmation of inflammatory findings in the lungs and overt aspiration or the existence of dysphagia. It is dominant in hospitalized community-acquired pneumonia (CAP), nursing and healthcare-associated pneumonia (NHCAP), and hospital-acquired pneumonia (HAP). The incidence of ASP is increasing every year. The human and experimental animal data revealed that micro-aspiration due to dysphagia during the night is the central mechanism of ASP. Therefore, the precise assessment of swallowing function is the key to diagnose ASP. From a therapeutic point of view, an appropriate administration of antibiotics, as well as a comprehensive approach for dysphagia plays a pivotal role in the prognosis and recovery from ASP. The non-pharmacologic approach, including swallowing rehabilitation and oral care, and a pharmacologic approach including ACE inhibitors and bronchodilators, are essential modalities for treatment and prevention of ASP. The clinical data of NHCAP provides us with a promising treatment strategy for ASP.
Topics: Aged; Animals; Community-Acquired Infections; Deglutition Disorders; Healthcare-Associated Pneumonia; Humans; Models, Animal; Pneumonia; Pneumonia, Aspiration
PubMed: 34782300
DOI: 10.1016/j.resinv.2021.09.012 -
Frontiers in Immunology 2021Immunotherapy that includes programmed cell death-1 (PD-1), programmed cell death- ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors has... (Meta-Analysis)
Meta-Analysis Review
Immunotherapy that includes programmed cell death-1 (PD-1), programmed cell death- ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors has revolutionized the therapeutic strategy in multiple malignancies. Although it has achieved significant breakthrough in advanced non-small cell lung cancer patients, immune-related adverse events (irAEs) including checkpoint inhibitor pneumonitis (CIP), are widely reported. As the particularly worrisome and potentially lethal form of irAEs, CIP should be attached more importance. Especially in non-small cell lung cancer (NSCLC) patients, the features of CIP may be more complicated on account of the overlapping respiratory signs compromised by primary tumor following immunotherapy. Herein, we included the previous relevant reports and comprehensively summarized the characteristics, diagnosis, and management of CIP. We also discussed the future direction of optimal steroid therapeutic schedule for patients with CIP in NSCLC based on the current evidence.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Complement System Proteins; Disease Management; Disease Susceptibility; Humans; Immune Checkpoint Inhibitors; Immune Checkpoint Proteins; Incidence; Lung Neoplasms; Lymphocyte Activation; Pneumonia; Prognosis; Severity of Illness Index; T-Lymphocytes
PubMed: 34122422
DOI: 10.3389/fimmu.2021.663986 -
Expert Review of Respiratory Medicine Nov 2020Bronchoalveolar lavage (BAL), a noninvasive, well-tolerated procedure is an important diagnostic tool that can facilitate the diagnosis of various lung diseases. This... (Review)
Review
INTRODUCTION
Bronchoalveolar lavage (BAL), a noninvasive, well-tolerated procedure is an important diagnostic tool that can facilitate the diagnosis of various lung diseases. This procedure allows the assessment of large alveolar compartments, by providing cells as well as non-cellular constituents from the lower respiratory tract. Alterations in BAL fluid and cells ratio reflects pathological changes in the lung parenchyma. In some cases, clinicians use BAL as a differential diagnosis guide for interstitial lung disease.
AREAS COVERED
In this review, we summarized the diagnostic criteria for BAL in interstitial lung diseases, pulmonary infections, lung cancer and other pathologies such as fat embolism, gastroesophageal reflux and collagen vascular disease. For this review, we have selected scientific papers published in the PubMed database in our area of interest. We aimed to highlight the usefulness of BAL in respiratory pathology.
EXPERT OPINION
Although BAL fluid analyzes has an essential role in the diagnostic work-up of many lung pathologies, it should be performed in selected patients. For accurate results, the BAL technique is very important to be standardized.
Topics: Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Connective Tissue Diseases; Diagnosis, Differential; Humans; Lung; Lung Diseases, Interstitial; Pneumonia
PubMed: 32847429
DOI: 10.1080/17476348.2020.1806063 -
Deutsche Medizinische Wochenschrift... Mar 2020
Topics: Germany; Healthcare-Associated Pneumonia; Humans; Pneumonia; Prognosis
PubMed: 32191974
DOI: 10.1055/a-0952-9509 -
JCO Oncology Practice Aug 2023Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is... (Review)
Review
Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer.
Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8% 34.1%; hazard ratio, 0.28; < .001), and in patients with HER2-low mBC treated with one prior line of chemotherapy (DESTINY-Breast04 [ClinicalTrials.gov identifier: NCT03734029]), T-DXd demonstrated significantly longer PFS and overall survival than physician's choice chemotherapy (10.1 5.4 months; hazard ratio, 0.51; < .001, and 23.4 16.8 months; hazard ratio, 0.64; < .001, respectively).Interstitial lung disease (ILD) is an umbrella term used for a group of diseases characterized by lung injury including pneumonitis, which can lead to irreversible lung fibrosis. ILD is a well-described adverse event associated with certain anticancer therapies, including T-DXd. An important part of T-DXd therapy for mBC consists of monitoring for and managing ILD. Although information on ILD management strategies is included in the prescribing information, additional information on patient selection, monitoring, and treatment can be beneficial in routine clinical practice. The objective of this review is to describe real-world, multidisciplinary clinical practices and institutional protocols used for patient selection/screening, monitoring, and management related to T-DXd-associated ILD.
Topics: Humans; Female; Breast Neoplasms; Antibodies, Monoclonal, Humanized; Immunoconjugates; Lung Diseases, Interstitial; Pneumonia
PubMed: 37207306
DOI: 10.1200/OP.22.00480 -
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