Citations

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly ( P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

The use of programmed cell death 1 ligand 1 (PD‐L1) as a predictive biomarker to select patients to receive programmed cell death 1 (PD‐1) or PD‐L1 inhibitors in non‐small cell lung cancer (NSCLC) is limited by the definitions of positivity, interassay agreement, and intra‐ and intertumoral heterogeneity of expression. Although PD‐L1 expression enriches for responses, the lack of expression does not exclude clinical benefit.

Objective To identify predictors of respiratory failure and to evaluate the therapeutic efficacy of plasma exchange (PE) and of rituximab versus cyclophosphamide in a cohort of patients with diffuse alveolar hemorrhage (DAH) secondary to antineutrophil cytoplasmic antibody–associated vasculitis (AAV) with or without respiratory failure. Methods We performed a single‐center historical cohort study of all consecutive patients with AAV‐associated DAH who were evaluated over a 16‐year period. Logistic regression models were developed to examine the predictive role of the baseline clinical characteristics for the development of respiratory failure, and for the effect of PE and remission induction therapy on the main outcome (complete remission at 6 months). Results Seventy‐three patients with DAH were identified, and 34 of them experienced respiratory failure. The degree of hypoxemia upon initial presentation, a higher percentage of neutrophils in the bronchoalveolar lavage fluid cell count, and higher C‐reactive protein levels were independently associated with the development of respiratory failure. PE was not associated with achieving complete remission at 6 months, with an odds ratio (OR) of 0.49 (95% confidence interval [95% CI] 0.12–1.95) ( P = 0.32). Rituximab treatment was independently associated with achieving complete remission at 6 months (OR 6.45 [95% CI 1.78–29], P = 0.003). Conclusion Our findings indicate that the most important predictor of respiratory failure in patients with DAH secondary to AAV is the degree of hypoxemia upon presentation. No clear benefit of the addition of PE to standard remission induction therapy was demonstrated. Complete remission by 6 months was achieved at a higher rate with rituximab than with cyclophosphamide in patients with DAH secondary to AAV, including those needing mechanical ventilation.