Evaluating and developing sealants for the prevention of pulmonary air leakage: A systematic review of animal models

Sealants may provide a solution for pulmonary air leakage (PAL), but their clinical application is debatable. For sealant comparison, standardized animal models are lacking. This systematic review aims to assess methodology and quality of animal models for PAL and sealant evaluation. All animal models investigating lung sealing devices (e.g., staplers, glues, energy devices) to prevent or treat PAL were retrieved systematically from Embase, Pubmed and Web of science. Methodological study characteristics, risk of bias, reporting quality and publication bias were assessed. A total of 71 studies were included ( N = 75 experiments, N = 1659 animals). Six different species and 18 strains were described; 92% of experiments used healthy animals, disease models were used in only six studies. Lesions to produce PAL were heterogenous, and only 11 studies used a previously reported technique, encompassing N = 5 unique lesions. Clinically relevant outcomes were used in the minority of studies (imaging 16%, air leak 10.7%, air leak duration 4%). Reporting quality was poor, but revealed an upward trend per decade. Overall, high risk of bias was present, and only 18.7% used a negative control group. All but one study without control groups claimed positive outcomes (95.8%), in contrast to 84.3% using positive or negative control groups, which also concluded equivocal, adverse or inconclusive outcomes. In conclusion, animal studies evaluating sealants for prevention of PAL are heterogenous and of poor reporting quality. Using negative control groups, disease models and quantifiable outcomes seem important to increase validity and relevance. Further research is needed to reach consensus for model development and standardization.