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Frontiers in Immunology 2023Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite... (Review)
Review
BACKGROUND
Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite numerous efforts to identify risk factors and develop predictive models, there is no clinically deployed risk prediction model for patient risk stratification or for guiding subsequent monitoring. We believe this is due to systemic suboptimal approaches in study designs and methodologies in the literature. The nature and prevalence of different methodological approaches has not been thoroughly examined in prior systematic reviews.
METHODS
The PubMed, medRxiv and bioRxiv databases were used to identify studies that aimed at risk factor discovery and/or risk prediction model development for ICI-induced pneumonitis (ICI pneumonitis). Studies were then analysed to identify common methodological pitfalls and their contribution to the risk of bias, assessed using the QUIPS and PROBAST tools.
RESULTS
There were 51 manuscripts eligible for the review, with Japan-based studies over-represented, being nearly half (24/51) of all papers considered. Only 2/51 studies had a low risk of bias overall. Common bias-inducing practices included unclear diagnostic method or potential misdiagnosis, lack of multiple testing correction, the use of univariate analysis for selecting features for multivariable analysis, discretization of continuous variables, and inappropriate handling of missing values. Results from the risk model development studies were also likely to have been overoptimistic due to lack of holdout sets.
CONCLUSIONS
Studies with low risk of bias in their methodology are lacking in the existing literature. High-quality risk factor identification and risk model development studies are urgently required by the community to give the best chance of them progressing into a clinically deployable risk prediction model. Recommendations and alternative approaches for reducing the risk of bias were also discussed to guide future studies.
Topics: Humans; Japan; Pneumonia; Risk Factors; Systematic Reviews as Topic
PubMed: 37818359
DOI: 10.3389/fimmu.2023.1228812 -
International Journal of Molecular... Aug 2019Human cytomegalovirus (HCMV) is an opportunistic pathogen causing disease mainly in immunocompromised patients or after congenital infection. HCMV infection of the... (Review)
Review
Human cytomegalovirus (HCMV) is an opportunistic pathogen causing disease mainly in immunocompromised patients or after congenital infection. HCMV infection of the respiratory tract leads to pneumonitis in the immunocompromised host, which is often associated with a bad clinical course. The related mouse cytomegalovirus (MCMV) likewise exhibits a distinct tropism for the lung and thus provides an elegant model to study host-pathogen interaction. Accordingly, fundamental features of cytomegalovirus (CMV) pneumonitis have been discovered in mice that correlate with clinical data obtained from humans. Recent studies have provided insight into MCMV cell tropism and localized inflammation after infection of the respiratory tract. Accordingly, the nodular inflammatory focus (NIF) has been identified as the anatomical correlate of immune control in lungs. Several hematopoietic cells involved in antiviral immunity reside in NIFs and their key effector molecules have been deciphered. Here, we review what has been learned from the mouse model with focus on the microanatomy of infection sites and antiviral immunity in MCMV pneumonitis.
Topics: Animals; Cytomegalovirus; Cytomegalovirus Infections; Disease Models, Animal; Disease Susceptibility; Host-Pathogen Interactions; Humans; Immunity; Pneumonia, Viral; Viral Tropism
PubMed: 31398860
DOI: 10.3390/ijms20163865 -
Journal of Medical Case Reports Nov 2022We report a case of acute respiratory distress associated with a histological pattern of acute fibrinous and organizing pneumonia, and discuss the possible...
BACKGROUND
We report a case of acute respiratory distress associated with a histological pattern of acute fibrinous and organizing pneumonia, and discuss the possible responsibility of flecainide therapy.
CASE PRESENTATION
A 61-year-old African woman developed a rapidly progressive dyspnea and required admission in the intensive care unit for orotracheal intubation and mechanical ventilation. Chest X-ray examination revealed bilateral infiltrates predominating in the basal part of both lungs. Lung computed tomography disclosed bilateral ground-glass opacities and septal thickening. After exclusion of the most common causes of infectious or immune pneumonia, a toxic origin was investigated and flecainide toxicity was considered. Lung biopsy was consistent with the unusual pattern of acute fibrinous and organizing pneumonia. Clinical and radiological improvement was noted after corticosteroid therapy, but the patient died from septic complications.
CONCLUSION
Flecainide-induced lung injury has rarely been reported in the literature and remains a diagnosis of exclusion. The histological pattern of acute fibrinous and organizing pneumonia has been previously observed with amiodarone. There are no firm guidelines for the treatment of acute fibrinous and organizing pneumonia, but some patients may positively respond to corticosteroids.
Topics: Female; Humans; Middle Aged; Flecainide; Pneumonia; Lung; Dyspnea; Biopsy; Cryptogenic Organizing Pneumonia
PubMed: 36320087
DOI: 10.1186/s13256-022-03619-w -
Immunology Feb 2020Host-microbiota interaction plays fundamental roles in the homeostasis of mucosal immunity. Dysbiosis of intestinal microbiota has been demonstrated to participate in... (Review)
Review
Host-microbiota interaction plays fundamental roles in the homeostasis of mucosal immunity. Dysbiosis of intestinal microbiota has been demonstrated to participate in various immune responses and many multifactorial diseases. Study of intestinal microbiota has moved beyond the consequences of dysbiosis to the causal microbiota associated with diseases. However, studies of pulmonary microbiota and its dysbiosis are still in their infancy. Improvement of culture-dependent and -independent techniques has facilitated our understanding of lung microbiota that not only exists in healthy lung tissue but also exerts great impact on immune responses under both physiological and pathological conditions. In this review, we summarize recent progresses of lung microbiota dysbiosis and its impact on the local immune system that determines the balance of tolerance and inflammation. We discuss the causal roles of pulmonary dysbiosis under disease settings, and propose that the interaction between lung microbiota and host is critical for establishing the immune homeostasis in lung.
Topics: Adaptive Immunity; Animals; Dysbiosis; Host-Pathogen Interactions; Humans; Immunity, Innate; Lung; Microbiota; Pneumonia
PubMed: 31631335
DOI: 10.1111/imm.13139 -
Advances in Respiratory Medicine May 2023A substantial increase in broad-spectrum antibiotics as empirical therapy in patients with community-acquired pneumonia (CAP) has occurred over the last 15 years. One of... (Review)
Review
A substantial increase in broad-spectrum antibiotics as empirical therapy in patients with community-acquired pneumonia (CAP) has occurred over the last 15 years. One of the driving factors leading to that has been some evidence showing an increased incidence of drug-resistant pathogens (DRP) in patients from a community with pneumonia, including methicillin-resistant (MRSA) and . Research has been published attempting to identify DRP in CAP through the implementation of probabilistic approaches in clinical practice. However, recent epidemiological data showed that the incidence of DRP in CAP varies significantly according to local ecology, healthcare systems and countries where the studies were performed. Several studies also questioned whether broad-spectrum antibiotic coverage might improve outcomes in CAP, as it is widely documented that broad-spectrum antibiotics overuse is associated with increased costs, length of hospital stay, drug adverse events and resistance. The aim of this review is to analyze the different approaches used to identify DRP in CAP patients as well as the outcomes and adverse events in patients undergoing broad-spectrum antibiotics.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Community-Acquired Infections; Pneumonia; Anti-Bacterial Agents
PubMed: 37366804
DOI: 10.3390/arm91030018 -
Chemico-biological Interactions Aug 2022In this Letter to the Editor supportive data were presented to a recent paper published in this journal reporting the involvement of TRP channels in COVID-19 pneumonia...
In this Letter to the Editor supportive data were presented to a recent paper published in this journal reporting the involvement of TRP channels in COVID-19 pneumonia and its role for new therapies. Since gene expression of TRP channels was found in human lung tissues the protein was not being reported so far. TRP channels are supposed to be involved in the pulmonary inflammation and its symptoms such as fever, cough and others. Here, TRPC6 was investigated in tissues of normal human lungs and of SARS-Cov-2 infected lungs in a preliminary study. Tissue was obtained post mortem from anatomical body donations during dissections and during pathological dissections (13 normal, 4 COVID-19 pneumoniae) and processed for immunohistochemistry. In normal lungs TRPC6 was found in the ciliated epithelium, in the wall of larger lung vessels and in the alveolar septa. In COVID-19 pneumonia the distribution of TRPC6 was different. Inflammatory lesions, cellular infiltrates, hyaline membranes and fibrosis were labelled intensively as well as dilated capillaries. These observations are from four patients with COVID-19 pneumonia.The observations do not elucidate the molecular mechanisms but support the view that TRPC6 channels are involved in normal physiology of normal human lungs and in COVID-19 pneumonia. TRPC6 might aggravate SARS-2 induced inflammation and could be a target for inhibiting drugs.
Topics: COVID-19; Humans; Lung; Pneumonia; SARS-CoV-2; TRPC6 Cation Channel
PubMed: 35598647
DOI: 10.1016/j.cbi.2022.109982 -
The Oncologist Jan 2024Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis.
MATERIALS AND METHODS
Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies.
RESULTS
Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028).
CONCLUSION
This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.
Topics: Humans; Aged; Carcinoma, Non-Small-Cell Lung; Retrospective Studies; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Kidney Neoplasms; Lung
PubMed: 37590388
DOI: 10.1093/oncolo/oyad187 -
Internal Medicine (Tokyo, Japan) Dec 2021We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab....
We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab. After 12 cycles, immune-related pneumonitis developed and was treated with prednisolone. Three months later, pancreatitis developed, which was successfully treated with hydration and protease inhibitors. Eight months later, another attack of pancreatitis occurred, which did not respond to therapy, including high-dose corticosteroids, and he eventually died. This is the first report describing fatal immune checkpoint inhibitor-related pancreatitis. Despite the rarity of this complication, attention should be paid to its potential severity and treatment.
Topics: Adrenal Cortex Hormones; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Pancreatitis; Pneumonia; Prednisolone
PubMed: 34121010
DOI: 10.2169/internalmedicine.7366-21 -
Revista Espanola de Quimioterapia :... Apr 2022We shall define occupational pneumonia as a disease of external origin, closely tied to the workplace setting and caused by biological microorganisms. The main pathogens... (Review)
Review
We shall define occupational pneumonia as a disease of external origin, closely tied to the workplace setting and caused by biological microorganisms. The main pathogens are bacteria, fungi and viruses. There are a number of occupations specifically prone to the possibility of acquiring pneumonia when performing work duties. In addition to the diagnostic methods and drug treatments current in infectious processes, a good clinical history, with avoidance and protection measures would be the most important tools for the management of occupational pneumonia. Social and demographic changes in the last two decades have made zoonotic infections, and especially viruses, the main cause of new infections. Human health and animal health are closely linked, so collaboration between veterinarians and doctors, together with the necessary environmental respect and conservation, plus the appropriate public policies are essential to avoid these wide negative effects.
Topics: Animals; Bacteria; Humans; Pneumonia; Zoonoses
PubMed: 35488834
DOI: 10.37201/req/s01.19.2022 -
BMC Cancer May 2022Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors...
BACKGROUND
Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors for pneumonitis, including smoking and lung metastasis (LM), in patients with extrapulmonary primary tumors.
METHODS
Data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for treating extrapulmonary primary tumors at the Shiga University of Medical Science Hospital between January 2015 and December 2019 were retrospectively collected. The association between the onset of pneumonitis and treatment-related factors was analyzed by logistic regression. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Risk factors, such as the absence or presence of interstitial lung disease (ILD) and LM, or other clinical factors, including smoking status before ICI administration, were analyzed.
RESULTS
Multivariate analyses indicated that the amount of smoking was significantly associated with an increase in the development of all-grade pneumonitis types (odds ratio (OR) = 20.33, 95% confidence interval (CI) = 20.03-20.66; p = 0.029). LM and ILD were significantly related to an increase in the development of symptomatic pneumonitis (≥ Grade 2) (OR = 10.08, 95% CI = 1.69-199.81; p = 0.076, and OR = 6.76, 95% CI = 1.13-40.63; p = 0.037, respectively).
CONCLUSIONS
Pre-screening for ILD and LM and recognizing patients' smoking history is important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.
Topics: Humans; Immune Checkpoint Inhibitors; Lung Diseases, Interstitial; Lung Neoplasms; Pneumonia; Retrospective Studies; Risk Factors
PubMed: 35578210
DOI: 10.1186/s12885-022-09642-w