Rationale: For spirometry interpretation, the European Respiratory Society (ERS) and American Thoracic Society (ATS) recommend using z-scores, and the ATS has recommended using Global Lung Initiative (GLI) “Global” race-neutral reference equations. However, these recommendations have been variably implemented, and the impact has not been widely assessed in clinical or research settings. Objectives: To evaluate the ERS/ATS classification of airflow obstruction severity. Methods: In COPDGene (Genetic Epidemiology of COPD Study) (N = 10,108), airflow obstruction has been defined by an FEV1/FVC ratio <0.70, with spirometric severity graded from class 1 to class 4 based on race-specific percent predicted (pp) FEV1 cutoff points as recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the GOLD approach, using National Health and Nutrition Examination Survey III race-specific equations, versus the application of GLI Global equations using the ERS/ATS definition of airflow obstruction as an FEV1/FVC ratio below the lower limit of normal and z-score–based FEV1 cutoff points of –1.645, –2.5, and –4 (“zGLI Global”). We tested the four-tier severity scheme for association with chronic obstructive pulmonary disease outcomes. Measurements and Main Results: The lowest agreement between ERS/ATS with zGLI Global and the GOLD classification was observed in individuals with milder disease (56.9% and 42.5% in GOLD stages 1 and 2, respectively), and race was a major determinant of redistribution. After adjustment for relevant covariates, zGLI Global distinguished all-cause mortality risk between normal spirometry and the first grade of chronic obstructive pulmonary disease (hazard ratio, 1.23; 95% confidence interval, 1.04–1.44; P = 0.014) and showed a linear increase in exacerbation rates with increasing disease severity in comparison with GOLD. Conclusions: The zGLI Global severity classification outperformed the GOLD criteria in the discrimination of survival, exacerbations, and imaging characteristics.

Background: The aim of this study was to assess diagnostic accuracy and reliability of narrow band imaging (NBI) in the differential diagnosis of laryngeal premalignant lesion, early cancers and recurrences. Material and methods: We enrolled 231 patients who underwent endoscopic examination with white light endoscopy (WLE) + NBI and divided them into two groups, group A, without previous radiochemotherapy and group B, with previous radiochemotherapy. When indicated, we performed surgical biopsies to evaluate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and likelihood of endoscopic examination comparing WLE alone and WLE + NBI. Results: A positive NBI lesion, compared with a negative NBI lesion, had a 29.68 (group A) and 13.96 (group B) times higher probability to be histologically positive (i.e., confirmed) compared with WLE alone improving the diagnostic accuracy. In group A, the NBI mode showed excellent sensitivity (95.0%), which was higher than WLE 2 mode (77.5%). However, the greatest differences were recorded regarding specificity (96.8% vs. 40.6%). In group B, both NBI alone and WLE + NBI mode showed a 94.1% specificity compared with WLE alone, which had a maximum specificity of 85.3%. The mode comparison between NBI and WLE in both groups showed a statistically significant difference, with p-values <0.0001. Conclusions: NBI represents a reliable technology in challenging situations, especially in the context of post-radiotherapy or post-surgical mucosal changes showing a high NPV. NBI could reduce the number of unnecessary biopsies related to increased microvascular anomaly revelation, which could help to identify early-stage lesions suitable for minimally invasive surgery and, consequently, decrease hospital admissions.

Mepolizumab represents an effective strategy for severe eosinophilic asthma. Small airways disease (SAD) defines a peculiar asthma phenotype related to worse disease control. Limited and indirect findings are currently available on the effect of mepolizumab on SAD. Objectives: We investigated the impact of mepolizumab on SAD assessed through impulse oscillometry (IOS) and spirometry. As secondary outcomes, we tested the correlation between SAD and clinical, functional and inflammatory parameters. Methods: This is a prospective cohort study including severe eosinophilic asthmatics eligible for mepolizumab performed between 2021 and 2023. IOS (R5–R20) and spirometry (FEF25-75%, TLC%, RV/TLC%) parameters were assessed at baseline and over 1 year of mepolizumab. Other functional (FEV1%), clinical (ACT, number of asthma exacerbations/previous year, use of OCS) and inflammatory data (BEC and FeNO) were concomitantly collected for correlations. Results: A total of 18 patients (mean age 61.1 ± 12.0 y; 10 (55.5%) female) were included. Longitudinal data from 16 patients showed that R5–R20 significantly improved after 12-months treatment (p: 0.03), as well as FEF25-75% (p: 0.04) and TLC% (0.04). FEV1% and ACT showed a concomitant improvement (p: 0.03 and <0.01, respectively). All the steroid-dependent subjects discontinued OCS after 3 months and the percentage of subjects experiencing exacerbations significantly decreased (p: <0.01). As per drug effect, BEC consistently decreased (p: <0.01). The decrease in R5–R20 correlated with an improvement in FEF25-75% (r: −0.40 p: 0.048) and ACT at T12 (r: −0.59 p: 0.02). Conclusions: Twelve months treatment with mepolizumab improved R5–R20, suggesting its additional role as a targeted treatment for distal lung regions. This improvement also correlated with a clinically relevant amelioration of asthma symptoms.

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that can cause fibrosis of the lung interstitium, resulting in respiratory failure and death. Patients with an ILD, particularly idiopathic pulmonary fibrosis (IPF) or connective tissue disease-associated ILDs (CTD-ILDs), are prone to develop chronic pulmonary infections such as tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD). Methods: This case series examines the management of three ILD patients with a usual interstitial pneumonia (UIP) pattern and concomitant NTM-PD or TB at National Institute for Infectious Diseases “Lazzaro Spallanzani” in Rome, Italy, over three years (2019–2022). Results and Conclusions: Multi-disciplinary discussion (MDD) was crucial to define the therapeutic approach due to the increased risk of side effects and drug interactions. Our work underscored how a comprehensive diagnostic evaluation, enriched by MDD, is useful for optimizing the management and reducing drug-related adverse effects and interactions in ILD patients with cavitary lesions.

Background: Blood eosinophil count is an accepted biomarker for type 2 inflammation in COPD. However, the majority of COPD patients are characterized by non-type 2 inflammation. We aimed to test readily obtainable immune cell ratios as biomarkers for clinical phenotypes in the broad COPD population and to determine pathways represented by these ratios using multi-omics data. Methods: Using complete blood counts with differential collected at the Phase 2 (5-year) visit in the COPDGene Study, we calculated three immune cell ratios previously described in COPD and other diseases: the neutrophil–lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the Systemic Immune-Inflammation Index (SII = NLR*platelets). We tested for associations with COPD outcomes, including lung function, chest CT scan phenotypes, and exacerbations. Blood RNA-sequencing and proteomics data were used to identify genes, proteins and pathways associated with the ratios. Results: In univariate analyses, the three biomarkers were associated with COPD severity measures. In zero inflated Poisson regression models, all three were associated with increased odds of having an exacerbation but were not associated with exacerbation counts. Conversely, the three biomarkers were generally associated with prospective exacerbation counts, but not the zero-inflation term. In logistic regression models, the three biomarkers were significantly associated with having two or more exacerbations in the prior year; however, receiver operating characteristic analyses did not lead to clear cutoff values. Complement and PI3K signaling pathways were enriched across more than one ratio in both the RNA-sequencing and proteomics results. Other inflammatory pathways relevant in COPD appeared in different enrichment sets in either omics data type. Conclusions: Higher levels of three easily obtained blood cell ratios were associated with COPD severity and exacerbations outcomes; however, there are not clear thresholds which would be required for clinical application. Blood RNA-sequencing and proteomics identified inflammatory pathways associated with the three biomarkers, including targets for COPD therapies currently in human trials.

Rationale: The European Respiratory Society (ERS) and the American Thoracic Society (ATS) recommend using z-scores and Global Lung Initiative (GLI) “Global” race-neutral reference equations for spirometry interpretation. However, the impact of those recommendations has not been widely implemented nor assessed, both in clinical and research settings. Objectives: We evaluated the ERS/ATS airflow obstruction severity classification. Methods: In the COPDGene Study (n = 10,108), airflow obstruction has been defined as a forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio <0.70, with spirometry severity graded from class 1 to 4 based on race-specific percent predicted (pp) FEV1 cut-points as recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared this approach to the application of GLI Global equations with airflow obstruction by FEV1/FVC< lower limit of normal and z-FEV1 cut-points of –1.645, –2.5, and –4. We tested the four-tier severity scheme for association with COPD outcomes. Measurements and Main Results: The lowest agreement between GLI Global and GOLD classification was observed in individuals with milder disease (56.9% and 42.5% in GOLD 1 and 2) and race was a major determinant of redistribution. After adjustment for relevant covariates, only GLI Global distinguished all-cause mortality risk between normal spirometry and the first grade of COPD (HR 1.23, 95% CI 1.04-1.44, p=0.014) and showed a linear increase in exacerbation rates with increasing disease severity, compared to GOLD. Conclusion: The GLI Global severity classification outperformed GOLD in the discrimination of survival, exacerbations and imaging characteristics.