Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene, leading to defective ion transport and impaired function of various organs. Chronic inflammation, oxidative stress, and microbial dysbiosis are key pathological features of CF patients, contributing to disease progression, lung damage, and an increased susceptibility to infections. Emerging evidence suggests that in CF patients these factors can promote cancer development, especially lung cancer. Chronic inflammation in CF, driven by immune cell dysfunction, results in the release of pro-inflammatory cytokines and reactive oxygen species (ROSs), fostering an environment conducive to cancer initiation. Oxidative stress can amplify cellular damage and hinder airway remodeling. ROSs not only damage cellular components such as lipids, proteins, and DNA but also disrupt lung homeostasis, creating a favorable environment for cancer development. Furthermore, the lung microbiome in CF patients is often dysbiotic, with a reduced diversity and the predominance of pathogenic bacteria such as Pseudomonas aeruginosa, which exacerbate inflammation and may contribute to carcinogenesis. This review explores the mechanisms linking CF to lung cancer, examining the potential clinical implications of these mechanisms for early detection, monitoring, and targeted therapies for lung cancer prevention in CF patients.

Over the last decade, immunotherapy has revolutionized lung cancer treatments, particularly in non-small cell lung cancer, where immune checkpoint inhibitors have achieved significant clinical success. However, high percentages of patients do not respond initially or eventually develop a resistance to these therapies. This review explores the evolution and challenges of immunotherapy in lung cancer, highlighting its clinical milestones and intrinsic and extrinsic resistance mechanisms. We investigate tumor-intrinsic resistance factors, including alterations in antigen presentation, the loss of Beta-2 microglobulin function, impaired interferon signaling, immune editing, epigenetic modifications, and tumor-extrinsic resistance, such as an immunosuppressive lung tumor microenvironment, dysregulated cytokine profiles, and the upregulation of immune checkpoints. Then, we focus on the emerging role of resistance biomarkers and the development of personalized treatment strategies to overcome these challenges. The complex interplay between tumor biology and immune modulation in lung cancer paves the way for novel approaches for improving the effectiveness of immunotherapeutic treatments.

Background: Small cell lung cancer (SCLC) is a malignant carcinoma characterized by high proliferative rate and early metastatization with limited treatment options and poor prognosis. The approval of ICIs has established a new standard of care for extensive-stage (ES)-SCLC (5). Atezolizumab, an anti PD-L1 monoclonal antibody, has been the first immune checkpoint inhibitor (ICI) to be approved for SCLC patients. This study aims to retrospectively evaluate the real-world effectiveness and safety of atezolizumab in a cohort of patients with ES-SCLC. Methods: We conducted a monocentric retrospective analysis of SCLC patients who received atezolizumab in addition to chemotherapy, between January 2020 and December 2023. Study design endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Results: A total of 134 patients were included in this study. Out of 134 patients who began the CEA protocol, 100 continued maintenance. Currently, 25 are alive, 17 still on atezolizumab, 5 on second-line therapy, and 3 receiving best supportive care. The median age was 65 years. Patients received a median of four cycles of CEA (range 1–6 cycles), while the median number of atezolizumab maintenance cycles was eight (range 0–75). The overall median survival was 15 months, with patients who received more than 30 cycles of atezolizumab showing OS of 46.7% at 48 months. Common adverse events included skin disorders, pneumonitis, colitis, alanine, and aspartate deaminase increment, dysthyroidism, and blood disorders with only 3% of patients experiencing grade 3 or higher toxicities. Conclusions: In this real-world cohort, atezolizumab demonstrated comparable effectiveness to clinical trial results, with a manageable safety profile. These findings support the use of atezolizumab as a viable treatment option for ES-SCLC in routine clinical practice.

Introduction: Emphysema is frequently observed in patients with fibrosing interstitial lung diseases (f-ILDs), leading to the clinical entity known as combined pulmonary fibrosis and emphysema (CPFE). This study aimed to evaluate the utility of airwave oscillometry (AOS) in detecting small-airway dysfunction (SAD) in patients with CPFE. Due to the coexistence of both restrictive and obstructive airway disease, spirometry is comparatively less sensitive in detecting airflow limitations in this population. Methods: A cohort of 52 patients with CPFE was recruited from Monaldi Hospital, Naples, between January and September 2023. Pulmonary function tests—including spirometry, body plethysmography, and single-breath diffusing capacity for carbon monoxide (DLCO)—were performed at baseline and following bronchodilator administration. Patients with normal FEV1/FVC ratios underwent airwave oscillometry (AOS) to assess respiratory system resistance (Rrs) and reactance (Xrs), with SAD defined as an R5–R19 value greater than 0.07 kPa·s·L⁻¹. Results: AOS-defined SAD was present in 40.4% (21/52) of the cohort. The R5–R19 value in the SAD group was 0.13 ± 0.05 kPa·s·L⁻¹, which can be compared to 0.04 ± 0.02 kPa·s·L⁻¹ in patients without SAD. Patients with SAD were more likely to be undergoing maintenance bronchodilator therapy (16/21; 76.2%) than those without SAD (8/31; 25.8%) (p = 0.015). Fourteen CPFE patients met the criteria for bronchial responsiveness. CPFE patients who responded to bronchodilators had lower R5-R19 values than non-responders (0.04 ± 0.02 vs. 0.09 ± 0.06 kPa·s·L⁻¹; p = 0.04). Discussion: Although AOS parameters did not significantly change following bronchodilator administration, this study underscores the value of AOS in detecting peripheral airway dysfunction, which may be under-recognized by conventional spirometry. Conclusions: AOS shows promise as a diagnostic adjunct for identifying SAD in CPFE patients and may complement standard pulmonary function testing in clinical practice. Further multicenter studies with larger cohorts are warranted to validate these findings and investigate the longitudinal impact of SAD on disease progression and treatment outcomes in CPFE.

Background/Objectives: Skeletal muscle wasting is a frequent and clinically consequential comorbidity in COPD, affecting 15–50% of patients and predicting reduced exercise tolerance, impaired quality of life, hospitalization, and mortality. However, no consensus exists on the optimal diagnostic approach, and the role of nutritional assessment remains underemphasized despite its contribution to muscle depletion. Methods: This narrative review synthesizes evidence from original research, systematic reviews, and consensus statements on diagnostic methods for evaluating muscle mass, strength, physical performance, and nutritional status in COPD. Results: Computed tomography and magnetic resonance imaging offer accurate assessment of muscle mass but are limited by cost and accessibility. Dual-energy X-ray absorptiometry provides a low-radiation alternative but cannot assess muscle quality. Bioelectrical impedance analysis and ultrasound are portable and inexpensive, yet lack standardized COPD-specific cut-offs. Functional tests provide clinically meaningful performance data but do not directly measure muscle mass. In parallel, nutritional screening tools and dietary assessment can identify modifiable risk factors and are associated with sarcopenia prevalence and prognosis in COPD. The choice of diagnostic approach significantly influences prevalence estimates. Conclusions: Optimal assessment of muscle wasting in COPD requires a multimodal approach combining muscle mass quantification, strength measurement, physical performance evaluation, and nutritional assessment. Standardized COPD-specific diagnostic criteria are needed. A practical algorithm integrating simple screening tools with targeted confirmatory assessments, including nutritional evaluation, may help guide clinical practice.