Pirfenidone and nintedanib are the only two drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF). Both proved to be safe and well-tolerated in clinical trials, but real-world data and direct comparisons are scarce. This real-life study explored the safety profile of pirfenidone and nintedanib with a prolonged follow-up. We retrospectively collected clinical status, adverse events (AEs), and treatment changes from IPF patients who had started an antifibrotic treatment at our centre from December 2011 to December 2020, including 192 patients treated with pirfenidone and 89 with nintedanib. The majority of patients in both groups experienced one or more AEs during the follow-up. A higher proportion of AEs in the nintedanib group were effectively treated with behavioural modifications or additional medications compared with the pirfenidone group (52.5% vs. 40.6%, p = 0.04). Overall, a difference in the impact of AEs due to nintedanib versus pirfenidone resulted in a lower permanent discontinuation of therapy (8.3% vs. 18.3%, p = 0.02), with the latter being associated with a higher risk of drug discontinuation at 48 months after initiation (OR = 2.52, p = 0.03). Our study confirms the safety profile of antifibrotic drugs in IPF but highlights that AEs due to nintedanib are usually easier to manage and lead to fewer cases of permanent discontinuation of therapy.

Background: High total IgE levels are weak predictors of T2_High and have been reported in nonallergic asthma. Therefore, the role of total serum IgE (IgE) in the T2_High phenotype is still debated. Objective: This study investigated the reliability of stratifying asthmatics into IgE_High and IgE_Low within the T2_High and T2_Low phenotypes. Methods: This cross-sectional single-center study investigated the association of clinical, functional, and bio-humoral parameters in a large asthmatic population stratified by IgE ≥ 100 kU/L, allergen sensitization, B-EOS ≥ 300/µL, and F_ENO ≥ 30 ppb. Results: Combining T2 biomarkers and IgE identifies (1) T2_Low-IgE_Low (15.5%); (2) T2_Low-IgE_High (5.1%); (3) T2_High-IgE_Low (33.6%); and T2_High-IgE_High (45.7%). T2_Low-IgE_Low patients have more frequent cardiovascular and metabolic comorbidities, a higher prevalence of emphysema, and higher LAMA use than the two T2_High subgroups. Higher exacerbation rates, rhinitis, and anxiety/depression syndrome characterize the T2_Low-IgE_High phenotype vs. the T2_Low-IgE_Low phenotype. Within the T2_High, low IgE was associated with female sex, obesity, and anxiety/depression. Conclusions: High IgE in T2_Low patients is associated with a peculiar clinical phenotype, similar to T2_High in terms of disease severity and nasal comorbidities, while retaining the T2_Low features. IgE may represent an additional biomarker for clustering asthma in both T2_High and T2_Low phenotypes rather than a predictor of T2_High asthma “per se”.

Background: Asthma exacerbation is episodic worsening of respiratory symptoms in conjunction with the deterioration of lung function, which may occur independently from the asthma severity hampering asthmatics’ quality of life. This study aimed to characterize the patient phenotype more prone to asthma exacerbation (oral corticosteroid burst ≥2 per year) to allow the proper identification of such patients. Methods: This real-life, observational, cross-sectional study evaluated 464 asthmatic patients stratified according to the asthma exacerbations experienced in the previous year. Clinical, functional, and blood parameters were retrieved from chart data and were representative of patients in stable conditions. Results: The frequent asthma exacerbator was more commonly female, suffered from chronic rhinosinusitis with nasal polyposis, had reduced lung function and peripheral oxygen saturation, and had increased daily activity limitations. These patients often had severe asthma and more frequently needed hospitalization in their lives. Furthermore, the frequent asthma exacerbator had higher concentrations of serum immunoglobulin E (IgE) and exhaled nitric oxide with cut-off risk values of 107.5 kU/L (OR = 4.1) and 43.35 ppb (OR = 3.8), respectively. Conclusions: This study illustrates the clinical features of the frequent asthma exacerbator phenotype. Nevertheless, serum IgE and exhaled nitric oxide could allow the identification of this phenotype and the establishment of an appropriate therapeutic approach.

Background: Concern may exist that pulmonary lesions associated with cystic airspaces are at risk of increased biopsy complications or lower biopsy accuracy given challenges in targeting tissue abutting or intermingled with the cystic airspaces. Objective: To evaluate the safety and diagnostic performance of CT-guided core-needle biopsy (CNB) of pulmonary lesions with cystic airspaces. Methods: This retrospective study included 90 patients (median age, 69.5 years; 28 female, 62 male) who underwent CT-guided CNB of pulmonary lesions associated with cystic airspaces (based on review of procedural images) from February 2010 to December 2022 and a matched control group (2:1 ratio) of 180 patients (median age, 68.0 years; 56 female, 124 male) who underwent CNB of noncystic noncavitary lesions during the same period. The groups were compared in terms of complications, nondiagnostic biopsies (i.e., nonspecific benignities, atypical cells, or insufficient specimens), and CNB diagnostic performance for detecting malignancy using as reference the final diagnosis from a joint review of all available records. For lesions associated with cystic airspaces that underwent surgical resection after CNB, histologic slides were re-reviewed to assess cystic airspace etiology. Results: The final diagnosis was malignant in 90% (81/90) of lesions associated with cystic airspaces and 92% (165/180) of noncystic noncavitary lesions. Patients with lesions associated with cystic airspaces and patients with noncystic noncavitary lesions showed no significant difference in frequencies of complication (all: 40% [36/90] vs 38% [68/180], p=.79; major: 4% [4/90] vs 6% [10/180], p=.78; minor: 36% [32/90] vs 32% [58/180], p=.59), frequency of nondiagnostic biopsies (12% [11/90] vs 9% [16/180], p=.40), or diagnostic performance (accuracy: 94.% [85/90] vs 97% [175/180], p=.50; sensitivity: 94% [76/81] vs 97% [160/165], p=.50; specificity: 100% [9/9] vs 100% [15/15]; p>.99), respectively. All false-negative results for malignancy in both groups occurred in patients with nondiagnostic CNB results. Among lesions associated with cystic airspaces that were resected after CNB (all malignant), the cystic airspaces most commonly represented tumor degeneration (22/31, 71%). Conclusion: CT-guided CNB is safe and accurate for assessing pulmonary lesions associated with cystic airspaces. Clinical Impact: CNB may help avoid a missed or delayed cancer diagnosis in pulmonary lesions with cystic airspaces.

Background: Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs. Objective: To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD. Methods: We measured the expression and localization of BMPs and some relevant antagonists in bronchial biopsies of stable mild/moderate COPD (MCOPD) (n = 18), severe/very severe COPD (SCOPD) (n = 16), control smokers (CS) (n = 13), and control non-smokers (CNS) (n = 11), and in lung parenchyma of MCOPD (n = 9), CS (n = 11), and CNS (n = 9) using immunohistochemistry and transcriptome analysis, in vitro after the stimulation of the 16HBE cells. Results: In bronchial biopsies, BMP4 antagonists CRIM1 and chordin were increased in the bronchial epithelium and lamina propria of COPD patients. BMP4 expression was decreased in the bronchial epithelium of SCOPD and MCOPD compared to CNS. Lung transcriptomic data showed non-significant changes between groups. CRIM1 and chordin were significantly decreased in the alveolar macrophages and alveolar septa in COPD patients. External 16HBE treatment with BMP4 protein reduced the bronchial epithelial cell proliferation. Conclusions: These data show an imbalance between BMP proteins and their antagonists in the lungs of stable COPD. This imbalance may play a role in the remodeling of the airways, altering the regenerative–reparative responses of the diseased bronchioles and lung parenchyma.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are mutually correlated with Type-2 inflammation. Dupilumab is effective in uncontrolled and relapsing CRSwNP. However, the precise characterization of Type-2 inflammation and the impact of previous surgery on clinical outcomes need clarification. Methods: We present a prospective observational study on a 38 CRSwNP-patient cohort, whose Type-2 endotype was confirmed after a multidisciplinary approach shared among ENTs, pneumologists and allergologists. Patients were treated with dupilumab and evaluated at 15 days and 1-3-6-12-18-24-30 months, focusing on clinical (VAS, nasal polyp score—NPS), radiological (Lund-Mackay) and quality of life (SNOT-22) parameters, as well olfactory function, asthma control, variation of Type-2 markers and number and extent (ACCESS score) of previous surgeries. Results: We confirmed the efficacy of dupilumab in total and sub-items VAS, NPS, SNOT-22 and sniffing score, as well as Lund–Mackay score improvements, observable and significant after 2 weeks of treatment (p < 0.0001) and long-lasting over 30 months. Good to excellent response criteria to biologic treatment at 6 months was observed in 30/32 patients. Comorbid asthma reached rapid control (p < 0.0001) and exhaled nitric oxide normalization was achieved. One single “not adequate” surgery showed a trend to milder improvement, as well as a higher ACCESS score to better olfactory outcome. Conclusions: The accurate selection of uncontrolled relapsing CRSwNP in terms of Type-2 endotyping by multidisciplinary approach can maximize dupilumab efficacy. The number and extent of previous surgeries may differentiate the response, although this effect is difficult to catch in real life. “Adequate” ESS surgery before dupilumab may drive mostly effective disease control.