Comparison of immune checkpoint inhibitors related to pulmonary adverse events: a retrospective analysis of clinical studies and network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed tumor treatment. However, the risk of pulmonary adverse events (PAEs) associated with ICI combination therapy is still unclear. We aimed to provide a PAE overview and risk ordering of ICIs used in tumor treatment. METHODS: We searched the databases of PubMed, PsycINFO, Embase, Cochrane Library, CINAHL, Web of Science, Scopus, and clinical trial websites during January 2011-April 2023 to identify phase II and III randomized clinical trials (RCTs) and single-arm clinical trials wherein at least one treatment arm received ICIs (e.g., ICI monotherapy, a combination of two ICIs, or ICIs in combination with conventional cancer therapy). We reported the results of PAEs. Additionally, we compared risks of PAEs between different drug classes using a Bayesian network meta-analysis. RESULTS: Among 143 RCTs and 24 single-arm trials, the incidence of all-grade and grade 3-4 PAEs were highest with programmed death L1 (PD-L1) plus cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and plus chemotherapy and anti-PD1 plus anti-CTLA4, the lowest with targeted therapy drug plus chemotherapy and anti-PD1 plus anti-PDL1. Anti-PD1 plus anti-CTLA4 and plus chemotherapy was the intervention with the highest risk for all-grade and 3-4 grade PAEs, and the intervention with the lowest risk was chemotherapy and anti-PD1 plus anti-PDL1. In terms of all-grade PAEs, chemotherapy was safer than ICI monotherapy. Except for the anti-PD1 plus anti-PDL1 regimen, no significant difference in the risk of grade 3-4 PAEs was detected between dual-ICIs and single-ICIs. Furthermore, the risk of PAEs associated with nivolumab, pembrolizumab, and atezolizumab may be dose dependent. CONCLUSIONS: In the single-drug regimen, anti-PD1 caused the greatest incidence of PAEs. The risk of PAEs was higher with all single-ICIs than with chemotherapy. However, no significant difference in the risk of PAEs was detected between single-ICIs. In the combined regimen, anti-PD1 plus anti-CTLA4 and plus chemotherapy showed the greatest risk of PAEs, but there were no significant differences in risk between dual-ICIs and single-ICIs.

Pulmonary adverse events of breast silicone implants and silicone injection.

The incidence of breast implants and silicone injections has continuously increased since their FDA approval for use in the 1960's. The prevalence of overall adverse events is approximately 20%. The actual incidence of pulmonary adverse events is unknown. This review focuses on the pulmonary adverse events of breast implants and silicone injections. Vascular complications are represented by acute and chronic embolisation syndromes with a clinico-radiological presentation of alveolar hemorrhage. Inflammatory complications are numerous, including siliconoma, which is a granulomatous reaction mimicking a mesothelioma. On the other hand, there are some reports arguing a link between the development of auto-immune diseases and breast implants, such as scleroderma, rheumatoid arthritis, Sjögren's syndrome, and dermatomyositis. Finally, for patients with asthma, breast implants may contribute to poor disease control. Cases of eosinophilic granulomatosis with polyangeitis have been described. Thus, it is of interest to decipherate mechanisms and incidence of these effects in prospective studies to better manage pulmonary diseases in patients wearing breast implants in order to understand their role as culprits or bystanders. In addition, characterization of subpopulations with increased risk of adverse events is needed as we highlighted that some subpopulations seem to be at greater risk of developing them, notably asthmatics.

Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components.

BACKGROUND: Platelet transfusion carries risk of transfusion-transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion-related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion. STUDY DESIGN: An open label, sequential cohort study of transfusion-dependent hematology-oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment-emergent assisted mechanical ventilation (TEAMV) by non-inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri-transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality. RESULTS: By modified intent-to-treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non-inferior to CPC for TEAMV (treatment difference -1.7%, 95% CI: (-3.3% to -0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p = .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p = .151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p = .256); and allergic TR were significantly less with PRPC (p = .006). PC and RBC use were not increased with PRPC. DISCUSSION: PRPC demonstrated reduced TEAMV with no excess treatment-related pulmonary morbidity.

Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis.

OBJECTIVES: Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical. METHODS: We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm. RESULTS: We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism. CONCLUSION: SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low.