-
Expert Review of Clinical Pharmacology 2023Serious phosphatidylinositol 3 kinase (PI3K) inhibitor-related pneumonitis has raised clinical concerns, and integrated data for this condition are lacking. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Serious phosphatidylinositol 3 kinase (PI3K) inhibitor-related pneumonitis has raised clinical concerns, and integrated data for this condition are lacking.
METHODS
Randomized controlled trials (RCTs) comparing PI3K inhibitor therapy with control treatments from electronic databases and registrations were searched from inception to 1 April 20231 April 2023seven1 April 2023. The outcomes of our study were the incidence and risk of all-grade and grade ≥ 3 PI3K inhibitor-associated pneumonitis compared with controls.
RESULTS
The meta-analysis included 13 studies comprising 3916 patients. The incidence of all-grade and grade ≥ 3 pneumonitis was 3.7% (82/2210) and 3.0% (35/1162) in patients treated with PI3K inhibitors. PI3K inhibitors significantly increased the risk of all-grade and grade ≥ 3 pneumonitis compared with controls (RR 5.63, 95% CI [2.97, 10.65], < 0.00001; RR 6.85, 95% CI [2.45, 19.11], = 0.0002, respectively) with no significant heterogeneity across studies. In terms of different PI3K inhibitors, copanlisib and idelalisib significantly increased the risk of pneumonitis compared to controls (RR 4.99, 95% CI [1.19, 21.01], = 0.03; RR 5.53, 95% CI [2.35, 13.01], < 0.0001, respectively).
CONCLUSION
PI3K inhibitors significantly increased the risk of pneumonitis compared with controls, and most cases are severe or even life-threatening.
PROSPERO REGISTRATION NUMBER
CRD42022318878.
Topics: Humans; Pneumonia; Phosphoinositide-3 Kinase Inhibitors; Incidence; Phosphatidylinositol 3-Kinases
PubMed: 37489925
DOI: 10.1080/17512433.2023.2238602 -
The European Respiratory Journal May 2020https://bit.ly/2XVwIsa
https://bit.ly/2XVwIsa
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Betacoronavirus; COVID-19; Coronavirus; Coronavirus Infections; Dyspnea; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32341100
DOI: 10.1183/13993003.01009-2020 -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409 -
Critical Reviews in Oncology/hematology Apr 2023Antibody-drug conjugates (ADCs) have demonstrated significant efficacy in treating solid tumors. However, the occurrence of ADC drug-associated pneumonitis can limit the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antibody-drug conjugates (ADCs) have demonstrated significant efficacy in treating solid tumors. However, the occurrence of ADC drug-associated pneumonitis can limit the use of ADCs or have severe consequences, and we know comparatively little about this.
METHODS
PubMed, EMBASE, and the Cochrane library were exhaustively searched for articles and conference abstracts published before September 30, 2022. Two authors independently extracted data from the included studies. A random-effects model was used to conduct a meta-analysis of the relevant outcomes. Forest plots reflected the incidence rates from each study, and binomial methods were used to calculate the 95 % confidence interval.
RESULTS
This meta-analysis included 7732 patients from 39 studies and evaluated the incidence of ADCs drug-associated pneumonitis which have received market approval for the treatment of solid tumors. The total incidence of solid tumors for all-grade pneumonitis was 5.86 % (95 % CI, 3.54-8.66 %) and for grade ≥3 was 0.68 % (95 % CI, 0.18-1.38 %). The incidence of all-grade pneumonitis was 5.08 % (95 % CI, 2.76-7.96 %) and for grade ≥3 was 0.57 % (95 % CI, 0.10-1.29 %) with ADC monotherapy. The incidence of all-grade and grade ≥3 pneumonitis in trastuzumab deruxtecan (T-DXd) was 13.58 % (95 % CI, 9.43-18.29 %) and 2.19 % (95 % CI, 0.94-3.81 %), respectively, the highest in ADC therapy. Total incidence of all-grade pneumonitis was 10.58 % (95 % CI, 4.34-18.81 %) and for grade ≥3 pneumonitis was 1.29 % (95 % CI, 0.22-2.92 %) with ADC combination therapy. The incidence of pneumonitis was higher with combination therapy than with monotherapy in both all-grade and grade ≥3 groups, but there was no statistical significance (P = .138 and P = .281, respectively). The incidence of ADC-associated pneumonitis in non-small cell lung cancer (NSCLC) was 22.18 % (95 % CI, 2.14-52.61 %), the highest among solid tumors. The 11 included studies reported 21 pneumonitis-related deaths.
CONCLUSIONS
Our findings will assist clinicians in choosing the optimal therapeutic options for patients with solid tumors treated with ADCs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Incidence; Lung Neoplasms; Pneumonia; Immunoconjugates
PubMed: 36907365
DOI: 10.1016/j.critrevonc.2023.103960 -
Expert Review of Vaccines 2023Community-acquired pneumonia (CAP) is an infectious lung inflammation contracted outside the hospital. CAP is a leading cause of death among young children, elderly, and... (Review)
Review
BACKGROUND
Community-acquired pneumonia (CAP) is an infectious lung inflammation contracted outside the hospital. CAP is a leading cause of death among young children, elderly, and immunocompromised persons. Incidence can reach 14 cases/1,000 adults. Up to 50% of cases require inpatient hospitalization. Mortality is 0.7/1,000 cases or 4 million deaths per year. We sought to summarize multi-dimensional burden of CAP for selected European countries.
METHODS
We conducted a systematic literature review of literature published from 2011 to 2021 whereby we sought information pertaining to the epidemiologic, clinical, economic, and humanistic burden of CAP. Findings were summarized descriptively.
RESULTS
CAP incidence in Europe is variable, with the highest burden among those of advanced age and with chronic comorbidities. Etiology is primarily bacterial infection with being the most frequently implicated. Direct medical costs are primarily attributable to inpatient stay, which is exacerbated among high-risk populations. Higher mortality rates are associated with increasing age, the need for inpatient hospitalization, and antibiotic resistance.
CONCLUSIONS
A better understanding of CAP is needed, specifically the economic and quality of life burden on patients and caregivers. We recommend further assessments using population-level and real-world data employing consistent disease definitions.
Topics: Adult; Child; Humans; Child, Preschool; Aged; Quality of Life; Pneumonia; Hospitalization; Streptococcus pneumoniae; Europe; Community-Acquired Infections
PubMed: 37823894
DOI: 10.1080/14760584.2023.2261785 -
Future Oncology (London, England) May 2023This study systematically evaluated cases of pneumonitis following combined immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) for locally advanced... (Meta-Analysis)
Meta-Analysis Review
This study systematically evaluated cases of pneumonitis following combined immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer (LA-NSCLC). Studies from Embase, PubMed and the Cochrane Library on patients with LA-NSCLC who received CRT and ICIs were reviewed. The primary outcomes were rates of all-grade, grade 3-5 and grade 5 pneumonitis. Overall, 35 studies involving 5000 patients were enrolled. The pooled rates of all-grade, grade 3-5 and grade 5 pneumonitis were 33.0% (95% CI: 23.5-42.6), 6.1% (95% CI: 4.7-7.4) and 0.8% (95% CI: 0.3-1.2), respectively, with 7.6% of patients discontinuing ICIs because of pneumonitis. The incidence rates of pneumonitis following combined CRT and ICIs for LA-NSCLC were acceptable. However, the pulmonary toxicity of concurrent CRT and nivolumab plus ipilimumab should be noted.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Chemoradiotherapy
PubMed: 37293787
DOI: 10.2217/fon-2022-1274 -
Diabetes Research and Clinical Practice Aug 2020COVID-19 pneumonia is a newly recognized illness that is spreading rapidly around the world and causes many disability and deaths. Some diseases, for instance diabetes,... (Review)
Review
BACKGROUND
COVID-19 pneumonia is a newly recognized illness that is spreading rapidly around the world and causes many disability and deaths. Some diseases, for instance diabetes, is continuously suggested as a risk factor which contributes to the severity and mortality of COVID-19. However, to date, there are no comprehensive studies aiming to explain the exact relationship between diabetes and COVID-19. Thus, this study aims to summarize the evidence about diabetes and COVID-19 outbreak through a systematic review and meta-analysis approach.
METHOD
A literature review was implemented within databases of Scopus, PubMed, Science direct, and Web of science. Observational reviews, case-report, and case-series studies that assessed the diabetes in COVID-19 patients, were included. Data extraction and assessment were guided by PRISMA checklist.
FINDINGS
Some studies suggest that there were no significant differences in symptoms between patients who suffered from both diabetes and COVID-19 and those who only suffered COVID-19. In the subsequent meta-analysis 14.5% of the subjects were diabetic patient. These clients have poor ARDS prognosis, severe symptoms, and the death rate is higher among COVID-19 patients. In addition, it is suggested the diabetic patients will be treated with antibiotics, antivirals, and HCQ.
CONCLUSION
The results of this study show that diabetes is a risk factor - and contributes to the severity and mortality of patients with COVID-19. This paper also provides recommendations and guidelines for which could be useful for prevention and treatment of diabetic patients affected by COVID-19.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Diabetes Mellitus; Humans; Pandemics; Pneumonia, Viral; Prognosis; Risk Factors; SARS-CoV-2
PubMed: 32711003
DOI: 10.1016/j.diabres.2020.108347 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809 -
Medicina (Kaunas, Lithuania) Sep 2020Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers.... (Review)
Review
Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.
Topics: Adolescent; Betacoronavirus; COVID-19; Child; Child, Preschool; Coronavirus Infections; Female; Humans; Lung; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 32942705
DOI: 10.3390/medicina56090474 -
Annals of Medicine Dec 2023To conduct a meta-analysis and systematic review on the association between anticholinergic medication uses and the risk of pneumonia in elderly adults. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis and systematic review on the association between anticholinergic medication uses and the risk of pneumonia in elderly adults.
MATERIALS AND METHODS
Medical databases were searched included PubMed, Web of Science, EBSCO and Google Scholar (up to December 7, 2022). Studies evaluating association between anticholinergic medication uses and the risk of pneumonia in elderly adults were included. Studies without available data were excluded. We made meta-analysis by using adjusted odds ratio (aOR) with 95% confidence intervals (CIs) from random-effects model. The risk of bias was assessed using ROBINS-I tool and statistical heterogeneity using the statistic. Registration: INPLASY202330070.
RESULTS
A total of six studies with 107,012 participants were included. Meta-analysis results showed that anticholinergic medication uses was related with an increased risk of pneumonia (aOR = 1.59; 95%CI, 1.32-1.92) and stroke-associated pneumonia (aOR = 2.02; 95%CI, 1.76-2.33). Moreover, risk estimates of pneumonia for high-potency anticholinergics (aOR = 1.96; 95%CI, 1.22-3.14) were higher than those for low-potency anticholinergics (aOR = 1.58; 95%CI, 1.27-1.97). And increased risk of pneumonia was associated with the anticholinergic medication uses within 30 days (aOR = 2.13; 95%CI, 1.33-3.43), within 90 days (aOR = 2.03; 95%CI, 1.26-3.26) and chronic use (aOR = 1.65; 95%CI, 1.09-2.51).
CONCLUSIONS
The risk of pneumonia is increased in elderly adults with anticholinergic medication, especially with higher-potency anticholinergic drugs and in the initiation phase of anticholinergic medication. Clinicians should monitor their use in older patients carefully, especially when the pneumonia-related signs and symptoms are identified.
Topics: Adult; Aged; Humans; Bias; Cholinergic Antagonists; Pneumonia
PubMed: 37190776
DOI: 10.1080/07853890.2023.2209736