No abstract

In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICI). The association of TMB with survival outside of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80% non-ICI-treated, 20% ICI-treated) with 17 cancer types, before/without ICI treatment, or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients, in whom higher TMB was associated with longer survival.

For over 150 years, bronchoscopy, especially flexible bronchoscopy, has been a mainstay for airway inspection, the diagnosis of airway lesions, therapeutic aspiration of airway secretions and transbronchial biopsy to diagnose parenchymal lung disorders. Its utility for the diagnosis of peripheral pulmonary nodules and therapeutic treatments besides aspiration of airway secretions, however, has been limited. Challenges to the wider use of flexible bronchoscopy have included difficulty in navigating to the lung periphery, the avoidance of vasculature structures when performing diagnostic biopsies and the ability to biopsy a lesion under direct visualization. The last 10-15 years has seen major advances in thoracic imaging, navigational platforms to direct the bronchoscopist to lung lesions and the ability to visualize lesions during biopsy. Moreover, multiple new techniques have either become recently available, or are currently being investigated to treat a broad range of airway and lung parenchymal diseases such as asthma, emphysema, chronic bronchitis or to alleviate recurrent exacerbations. New bronchoscopic therapies are also being investigated to not only diagnose, but possibly treat malignant peripheral lung nodules. As a result, flexible bronchoscopy is now able to provide a new and expanding armamentarium of diagnostic and therapeutic tools to treat patients with a variety of lung diseases. This state-of-the-art review succinctly reviews these techniques and provides clinicians an organized approach to their role in the diagnosis and treatment of a range of lung diseases.

Background: The coronavirus disease 2019 (COVID-19) has been identified in over 110 million people with no studies comparing pre-infection pulmonary function to post-infection. This study's aim was to compare preinfection and post-infection pulmonary function tests (PFT) in COVID-19 infected patients to better delineate between preexisting abnormalities and effects of the virus. Methods: This was a retrospective multi-center cohort study. Patients were identified based on having COVID-19 and a pre-and post-infection PFT within one year of infection during the time period of March 1, 2020 to November 10, 2020. Findings: There was a total of 80 patients, with an even split in gender; the majority were white (n = 70, 87¢5%) and never smokers (n = 42, 52¢5%). The majority had mild to moderate COVID-19 disease (n = 60, 75¢1%) with 25 (31¢2%) requiring hospitalization. There was no difference between the pre-and post-PFT data, specifically with the forced vital capacity (FVC) (p = 0¢52), forced expiratory volume in 1 s (FEV1) (p = 0¢96), FEV1/FVC(p = 0¢66), total lung capacity (TLC) (p = 0¢21), and diffusion capacity (DLCO)(p = 0¢88). There was no difference in the PFT when analyzed by hospitalization and disease severity. After adjusting for potential confounders, interstitial lung disease (ILD) was independently associated with a decreased FEV1 (-2¢6 [95% CI, -6¢7 to -1¢6] vs. -10¢3 [95% CI, -17¢7 to -2¢9]; p = 0¢03) and an increasing age (p = 0¢01) and cystic fibrosis (-1¢1 [95% CI, -4¢5 to-2¢4] vs. -36¢5 [95% CI, -52¢1 to -21¢0]; p < 0¢01) were associated with decreasing FVC when comparing pre and post infection PFT. Only increasing age was independently associated with a reduction in TLC (p = 0¢01) and DLCO (p = 0¢02) before and after infection. Interpretation: This study showed that there is no difference in pulmonary function as measured by PFT before and after COVID-19 infection in non-critically ill classified patients. There could be a relationship with certain underlying lung diseases (interstitial lung disease and cystic fibrosis) and decreased lung function following infection. This information should aid clinicians in their interpretation of pulmonary function tests obtained following COVID-19 infection.