Biological drugs have revolutionized the management of severe asthma. However, a variable number of patients remain uncontrolled or only partially controlled even after the appropriate administration of a biologic agent. The combination of two biologics may target different inflammatory pathways, and it has been used in patients suffering from uncontrolled severe asthma with evidence of both allergic and eosinophilic phenotypes or severe asthma and type2 comorbidities. Combination therapy has also been used to handle anti-IL4/13R induced hypereosinophilia. There is insufficient data on combining biologics for the treatment of severe uncontrolled asthma and type 2 comorbidities, also because of the high cost, and currently no guideline recommends dual biologic therapy. A systematic search was performed using the Medline and Scopus databases. Published data on concurrent administration of two biological drugs in severe, uncontrolled asthma patients has been reported in 28 real-world studies and 1 clinical trial. Data extraction was followed by a descriptive and narrative synthesis of the findings. Future studies should be conducted to further assess the safety, efficacy, and cost-effectiveness of this therapeutic strategy.

Interstitial lung diseases (ILDs) encompass a heterogeneous group of disorders characterized by varying degrees of inflammation and fibrosis. Despite advances in understanding the pathogenesis, therapeutic options remain limited, particularly for patients with progressive phenotypes. Current international guidelines for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) emphasize the need for antifibrotic strategies and call for novel pharmacological interventions targeting key molecular pathways involved in fibrogenesis. This review provides a comprehensive overview of the most promising emerging pharmacological agents for ILDs, with particular attention to their mechanisms of action, efficacy, and safety profiles as reported in recent preclinical and clinical studies. The recent approval of Nerandomilast and the ongoing phase III trials of other agents mark a pivotal transition toward a new generation of antifibrotic therapies, aiming to achieve more effective disease control and improved patient outcomes. In view of an enlargement of active drugs aiming at controlling the disease with different mechanisms, the Authors underline the need for a “precision medicine” model to be applied to each ILD phenotyped patient, mirroring what already happens for other respiratory diseases.

Severe asthma exacerbations have high morbidity and mortality. The management can be challenging, and the optimal strategy for patients admitted to the intensive care unit (ICU) with life-threatening and near-fatal asthma has not been fully defined. An interesting area of research is represented by the rescue or compassionate use of biological drugs when all treatments fail, including advanced interventions such as extracorporeal membrane oxygenation. This systematic review analyzes the cases described in the literature and discusses characteristics, treatments, and outcomes of patients who received asthma-approved monoclonal antibodies as rescue therapy following admission to the ICU due to near-fatal asthma exacerbations or status asthmaticus refractory to conventional treatments. A total of 14 studies (13 case reports and 1 case series) were included according to the prespecified inclusion and exclusion criteria. Various monoclonal antibodies were administered, most commonly benralizumab and omalizumab. Treatment was generally initiated within the first week of ICU admission, with nearly half of the patients receiving therapy within 5 days. Further research, including randomized controlled trials, is required to assess if this therapeutic option impacts ICU outcomes, which specific biologics could be used, and their eventual optimal timing and dosage.

Purpose of Review: To review current evidence on biologic therapies targeting type 2 inflammation in patients with eosinophilic COPD and respiratory comorbidities who remain uncontrolled despite optimized triple inhaled therapy. Recent Findings: Recent phase 3 trials have shown that dupilumab provides the most consistent benefit in eosinophilic COPD, reducing exacerbations and improving lung function and quality of life. Mepolizumab has shown a more limited effect, mainly on exacerbation reduction, whereas benralizumab has not demonstrated clear clinical benefit. Blood eosinophil count remains the main biomarker for treatment selection. Summary: Biologic therapies are advancing precision medicine in COPD, with dupilumab currently showing the strongest overall evidence. Careful patient selection is essential. Broader phenotyping may further improve management, as comorbidities such as chronic rhinosinusitis may contribute to symptom burden and support a multidisciplinary approach. Future studies should clarify long-term outcomes and optimal biologic selection.

Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is one of the most challenging events in the disease course due to the high mortality despite treatment. The role of corticosteroid treatment in AE-IPF has never been defined, even though it is used in current clinical practice. We performed a meta-analysis to determine the effects of steroid treatment on the acute exacerbation outcomes in idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate the impact of steroids on mortality in patients affected by an acute exacerbation of IPF. Methods: This meta-analysis was performed in accordance with the PRISMA statement. A systemic literature search was conducted through Google Scholar, Scopus, WoS, PubMed, and JSTOR. Manuscripts from January 2014 to September 2024 were included in the analysis. Articles were included on whether participants had an acute exacerbation of IPF. Regarding the intervention performed, we evaluated the studies in which patients underwent treatment with corticosteroids. As outcomes, studies were included if they analyzed the overall mortality. Results: A total of 2156 records were initially identified. Nineteen studies (3277 patients) were ultimately included in the final analysis, comparing 1552 patients who received steroids to 1725 patients without steroids. Steroid treatment poses a higher risk, as suggested by the summary measures (RR of 1.78; CI 1.29–2.76, p = 0.00001). Conclusions: This meta-analysis investigated the debated role of corticosteroid treatment during acute exacerbation of idiopathic pulmonary fibrosis. Overall, steroid therapy is associated with increased risk. Clinicians should carefully weigh the risks and benefits of corticosteroid therapy in acute exacerbation of IPF.

Background: Airway mucus plugging is a key but long-overlooked mechanism of persistent airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Type 2 (T2) cytokines, particularly interleukin (IL)-4 and IL-13, drive goblet cell metaplasia, MUC5AC overexpression, and impaired mucociliary clearance, while eosinophil-derived products increase mucus viscosity and promote plug persistence. Methods: A comprehensive narrative review was conducted by searching PubMed and ClinicalTrials.gov databases from inception to February 2026. Search terms included “mucus plugs,” “mucus plugging,” “biologics,” “dupilumab,” “tezepelumab,” “mepolizumab,” “benralizumab,” “IL-4,” “IL-13,” “MUC5AC,” “quantitative CT,” “functional respiratory imaging,” “asthma,” and “COPD.” Studies were included if they reported original data or systematic evidence on mucus plug quantification, biologic-mediated changes in mucus plug scores, or imaging modalities for mucus assessment in asthma or COPD. Editorials, case reports with fewer than three patients, and studies not available in English were excluded. Two authors (P.-V.M. and A.C.) independently screened titles and abstracts; discrepancies were resolved by consensus. Randomized controlled trials, observational studies, and preclinical studies evaluating mucus plug outcomes and T2-targeted therapies were included. Reference lists of retrieved articles were hand-searched for additional relevant publications. Results: A recent systematic review identified multiple randomized controlled trials and observational studies that showed CT-assessed mucus plug scores go down with biologic therapies targeting the T2 pathway in asthma. Observational data extend this evidence to anti-IL-5/IL-5Rα agents. The VESTIGE trial provided the first functional respiratory imaging evidence of mucus plug resolution with dupilumab. In COPD, the BOREAS/NOTUS and MATINEE trials established the efficacy of dupilumab and mepolizumab in eosinophilic phenotypes; however, differences in inclusion criteria—particularly regarding FeNO thresholds and prior exacerbation burden—may explain divergent effects on lung function endpoints. Mucus plug outcomes have not been evaluated in COPD biologic trials. Quantitative imaging modalities, including HRCT mucus plug scoring, functional respiratory imaging, and hyperpolarized gas MRI, now enable objective assessment of mucus burden. Conclusions: Mucus plugging meets the definition of a treatable trait: it can be measured with CT scoring, it matters clinically, and it responds to T2 cytokine blockade. Adding mucus plug assessment to routine clinical evaluation, together with mucolytic strategies where needed, could move treatment decisions from empirical to biology-based across the asthma–COPD spectrum. Further studies are needed to confirm that mucus plug scoring works as a biomarker of treatment response in COPD and to test whether combining biologics with mucolytics improves outcomes.