Search Results (49)

The therapeutic goals related to chronic airway diseases are evolving from short-term symptom control toward sustained suppression of disease activity and prevention of future risk. In severe asthma, this shift has been captured by the concept of clinical remission, generally defined by absence of exacerbations, no need for oral corticosteroids, symptom control, and stable or improved lung function. In chronic obstructive pulmonary disease (COPD), the analogous concept has more often been described as disease stability. Although remission in asthma and stability in COPD have developed within different biological and clinical frameworks, they may reflect disease-specific expressions of the same therapeutic ambition. Recent studies support COPD stability as a measurable and clinically meaningful state, associated with reduced exacerbation risk and mortality. Evidence from optimized inhaled triple therapy, particularly with fluticasone furoate/umeclidinium/vilanterol, indicates that multidimensional stability can be achieved and maintained in a proportion of patients, while real-world studies reinforce its applicability beyond randomized trials. The emergence of biologic therapies for selected patients with eosinophilic or type 2 COPD further strengthens the rationale for considering stability as an ambitious treatment target. In this narrative review, informed by a structured literature search, we discuss the conceptual relationship between asthma remission and COPD stability, and summarize the evidence supporting disease stability as an attainable and prognostically relevant outcome. In addition, we propose a pragmatic multidimensional definition based on symptom stability, absence of moderate or severe exacerbations, no systemic corticosteroid use, and maintained lung function over 12 months. COPD stability should not be viewed as a weaker goal than asthma remission, but rather as the most appropriate COPD-specific expression of sustained low disease activity. Full article

Paediatric rhinosinusitis (RS), particularly chronic rhinosinusitis (CRS), is a common inflammatory condition with a significant impact on quality of life and a well-recognized association with asthma within the framework of united airway disease. This review aims to evaluate the impact of RS, mainly CRS, on asthma control in children and explore its role as a modifiable determinant. Mechanistically, RS and asthma share key pathophysiological features, including type 2 inflammation, epithelial barrier dysfunction, and airway microbiome dysbiosis, supporting the concept of a unified inflammatory process across the respiratory tract. Clinically, epidemiological data demonstrate a high prevalence of coexisting RS and asthma, with consistent associations with poorer asthma control, increased disease severity, and higher exacerbation burden, even in cases of subclinical sinonasal inflammation. Available observational evidence suggests that appropriate management of CRS, including medical therapy and, in selected cases, surgical intervention, may improve asthma outcomes such as symptom control and lung function. Targeted biologic therapies have shown clinical benefit in adolescents with CRS with nasal polyps (CRSwNP) and high type 2 inflammation, although paediatric data remain limited. However, the existing evidence is predominantly based on small, heterogeneous, observational studies. RS therefore represents a potentially treatable trait in paediatric asthma, warranting systematic evaluation in children with difficult-to-treat disease. Further prospective and interventional studies are needed to clarify causality and define the impact of RS on long-term outcomes. Full article

Background: Dupilumab, a monoclonal antibody blocking IL-4Rα, has recently demonstrated efficacy in patients with type 2 (T2)-inflamed chronic obstructive pulmonary disease (COPD) in the BOREAS and NOTUS trials. Real-world experience in older patients with predominant chronic bronchitis phenotype remains limited. Methods: We report a single-centre case series of 12 consecutive patients with T2-inflamed COPD treated with dupilumab 300 mg every two weeks under a compassionate-use programme at San Carlo di Nancy Hospital, Rome (first administration: April 2025). Eligibility required ≥2 moderate or ≥1 severe exacerbation in the prior 12 months despite triple inhaled therapy and a blood eosinophil count ≥300 cells/µL. Follow-up ranged from 3 to 12 months, with 6 months pre-specified as the primary analysis timepoint; data at 9 and 12 months are reported as descriptive observations. Endpoints included paired changes in annualised exacerbation rate (AER), CAT score and item-level CAT, and FEV₁, with exploratory univariate Spearman analyses of candidate baseline predictors of response. Results: The cohort was elderly (mean age 73.6 ± 5.2 years, range 65–82), predominantly female (8/12, 67%) and characterised by a chronic bronchitis phenotype with high symptom burden (mean baseline CAT 22.8 ± 7.5; CAT item 2 [phlegm] median 3, IQR 3–4). Severe exacerbations decreased significantly (Wilcoxon p = 0.0156; mean AER 0.75 → 0.19 events/patient-year; 6/12 improved, 0/12 worsened). The mean cumulative function showed a standardised incidence ratio of 0.46 (95% CI 0.19–0.95; p = 0.033) versus the pre-dupilumab rate. Mean FEV₁ increased by +66 mL at 1 month (n = 11, paired Wilcoxon p = 0.025), +78 mL at 3 months (n = 10, p = 0.082) and +120 mL at 6 months (n = 10, p = 0.007). Total CAT decreased from 22.9 to 12.5 at 6 months (Friedman p = 0.0007), with the largest absolute reductions in item 2 (phlegm; Δ = −2.6 at 6 months, p < 0.001) and item 3 (chest tightness; Δ = −2.5 at 6 months, p = 0.002). Higher baseline CAT was associated with greater reduction in severe AER (Spearman ρ = −0.79, p = 0.002). Conclusions: In this elderly real-world cohort with phlegm-driven T2 COPD, dupilumab was associated with a significant decrease in severe exacerbations, a clinically meaningful gain in lung function and a marked improvement in mucus-related symptoms. Further studies are warranted to confirm these findings and to clarify whether the reduction in severe exacerbations translates into a measurable mortality benefit. Full article

Non-cystic fibrosis bronchiectasis (NCFB) is a heterogeneous chronic airway disease characterized by irreversible bronchial dilatation, impaired mucociliary clearance, and recurrent infection. Historically, research and clinical practice have focused mainly on bacteria, particularly Pseudomonas aeruginosa, as major drivers of exacerbations and disease progression, whereas the contribution of fungi has received far less attention. Over the last decade, evidence from mycobiome studies, large registries, and prospective cohorts has increasingly identified Aspergillus spp. as clinically relevant contributors in a substantial subset of patients with bronchiectasis. Data from the European Bronchiectasis Registry (EMBARC) indicate that approximately one quarter of patients exhibit Aspergillus-related immunological signals, including allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization, and elevated Aspergillus-specific IgG, and that these phenotypes are associated with more severe disease and worse clinical outcomes. Mechanistic studies further suggest that Aspergillus-related disease in bronchiectasis is underpinned by distinct molecular and immunological programs involving epithelial dysfunction, impaired mucociliary clearance, innate fungal sensing, inflammasome-related signaling, and divergent type-2 versus non-type-2 inflammatory responses. In parallel, mycobiome and multi-biome studies indicate that Aspergillus should be interpreted within a broader airway interactome shaped by cross-kingdom relationships with bacterial pathogens and by host immune tone. In this review, we synthesize current evidence on the epidemiology, molecular pathobiology, inflammatory endotypes, biomarker profiles, clinical–radiologic spectrum, and therapeutic implications of Aspergillus in bronchiectasis. Current evidence suggests that Aspergillus-related findings in bronchiectasis should be interpreted within a structured clinical, radiological, microbiological, and immunological framework rather than considered solely as isolated culture results. However, most data remain observational or extrapolated from related airway diseases, and bronchiectasis-specific interventional evidence is limited. A cautious biomarker-informed approach may help standardize phenotyping, identify patients requiring closer follow-up, and define priorities for future prospective trials. Full article

Background: The factors contributing to physical inactivity in patients with asthma remain unclear. We aimed to explore the pulmonary and extra-pulmonary factors associated with physical activity (PA) in these patients, with stratification by activity intensity. Methods: Patient demographics, Charlson Comorbidity Index, lung function, bronchial and alveolar nitric oxide (NO) levels, six-minute walk test (6 MWT), and PA were cross-sectionally evaluated in healthy participants (n = 14) and patients with asthma (n = 29). The desaturation–distance ratio (DDR) was measured as an index derived from travel distance and desaturation levels during the 6 MWT. Results: Patients with asthma had significantly lower PA than healthy participants, regardless of activity intensity (≥2 metabolic equivalents [METs]: 198 min vs. 240 min, p < 0.05; ≥3 METs: 54 min vs. 86 min, p < 0.05; ≥4 METs: 10 min vs. 26 min, p < 0.01). Extra-pulmonary factors (age, comorbidities, and 6 MW distance) showed higher correlation coefficients with PA as activity intensity increased. Contrastingly, pulmonary factors (asthma severity, airflow limitation, and alveolar exhaled NO) showed lower correlation coefficients with PA as activity intensity increased. The DDR was negatively associated with active time across all activity intensities. Conclusions: Our findings suggest that aging and comorbidities are potential limiting factors for moderate-to-vigorous physical activity, whereas asthma severity and airway dysfunction restrict daily life in patients with asthma. Moreover, the DDR could facilitate detection of real-life physical inactivity in patients with asthma. Full article

Acute respiratory failure (ARF) often leads to ICU admission, ventilatory support, illness, and death. The usual classification into hypoxemic and hypercapnic types does not capture its full complexity. Precision medicine uses the concept of “treatable traits” to guide care based on traits that are clinically relevant, identifiable, measurable, and possibly changeable. Arterial carbon dioxide pressure (PaCO₂) reflects factors like alveolar ventilation, dead space, respiratory mechanics, and how patients respond to ventilatory support. This makes it clinically relevant in selected situations. We carried out a scoping review using PRISMA-ScR and JBI guidelines to summarize evidence on hypocapnia and hypercapnia as prognostic, stratification, or clinically relevant variables during respiratory support. We searched PubMed/MEDLINE, ScienceDirect, and Web of Science (1994–2025), and checked references by hand. Thirty-four studies met our criteria and were grouped into four areas: pre-intubation or early acute presentation, non-invasive support (NIV/HFNC), invasive mechanical ventilation (IMV), and weaning or post-extubation. In summary, hypocapnia was linked to worse outcomes or failure of support in hypoxemic or cardiogenic cases. Hypercapnia helped identify patients who benefited from NIV, such as those with chronic obstructive pulmonary disease or obesity hypoventilation. For IMV, the effects depended on the presence and severity of acidosis and on its duration. Overall, PaCO₂ showed context-dependent clinical relevance, acting mainly as a prognostic or stratification marker and, in narrower settings, as a variable that may inform monitoring or support decisions. This review provides a pragmatic framework for interpreting PaCO₂ across respiratory support contexts and highlights the need for safe and clinically meaningful targets. Full article

Asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are major non-communicable respiratory diseases (NCD-RDs) with high morbidity and mortality. Despite distinct clinical features, they share overlapping mechanisms including oxidative stress, epithelial injury, and immune dysregulation. Asthma is mainly driven by type 2 inflammation, with IL-4, IL-5, and IL-13 inducing eosinophilia, IgE production, mucus hypersecretion, and airway remodeling. Biologics targeting IgE, IL-5, and IL-4Rα have transformed treatment, and agents directed against TSLP and IL-33 further extend the range of targeted interventions. In contrast, COPD involves chronic inflammation with macrophages, neutrophils, and CD8+ T cells, persisting after smoking cessation. Advances include biologics such as dupilumab and benralizumab in eosinophilic COPD, and novel inhaled therapies such as ensifentrine, the first dual PDE3/4 inhibitor delivered via inhalation. IPF, on the other hand, arises from defective epithelial repair and fibroblast activation, causing progressive fibrosis. Approved antifibrotics (nintedanib, pirfenidone) slow lung function decline, while new strategies target TGF-β, CTGF, and fibroblast-directed pathways. Across these diseases, biomarkers and the treatable traits framework are reshaping precision care. Personalized approaches integrating biomarkers, omics, and targeted therapies represent the most promising path for improved outcomes. Full article

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. Full article

Chronic obstructive pulmonary disease (COPD) represents an escalating global health challenge characterized by profound clinical and biological heterogeneity. Conventional diagnostic paradigms, primarily reliant on spirometric criteria and broad phenotypic labels, often fail to capture the complex molecular mechanisms underlying effective precision medicine. This narrative review synthesizes the evolving landscape of COPD characterization, analyzing the integration of biomarkers, advanced quantitative imaging, and multi-omics technologies. Key developments highlighted include the clinical validation of biologics targeting type 2 inflammation, which reinforce the paradigm shift from generic symptomatic management toward the identification of specific treatable traits. We further explore the role of artificial intelligence and deep learning in enhancing radiological precision and body composition analysis. Ultimately, this work proposes a transition toward a GETomics (Genetics, Environment, and Time) framework as a fundamental prerequisite for transcending the limitations of traditional classification systems and delivering truly personalized care in the 21st century. Full article

The concept of united airway disease (UAD) highlights the bidirectional relationship between inflammatory disorders of the upper airways—such as allergic rhinitis and chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP)—and lower airway diseases, most notably asthma. This paradigm is supported by epidemiological, embryological, and immunological evidence demonstrating that airway inflammation represents a single, interconnected process rather than isolated compartmental pathology. Central to many UAD phenotypes is type 2 (T2) inflammation, driven by cytokines including IL-4, IL-5, and IL-13, and mediated by effector cells such as eosinophils and group 2 innate lymphoid cells (ILC2s). Epithelial barrier dysfunction often serves as the initiating trigger for this shared inflammatory cascade by production of TSLP, IL-25 and IL-33. Optimal diagnosis and management of UAD require an integrated, multidisciplinary framework. Clinical evaluation remains essential for patient characterization but must be complemented by pheno-endotypic assessment using imaging (CT), allergy testing, biomarker profiling (FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, impulse oscillometry). Therapeutic strategies are layered, targeting both symptom control and inflammation across airway compartments. Standard approaches include intranasal and inhaled corticosteroids as well as saline irrigations, while severe T2-high disease increasingly benefits from biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP), which reduce dependence on systemic corticosteroids and surgical interventions such as endoscopic sinus surgery (ESS). Emerging precision-medicine models, particularly the “treatable traits” approach, further underscore the need to view the airway as a unified system. Collectively, these insights reinforce the clinical imperative of addressing upper and lower airway disease as a continuum, ensuring that inflammation in one district is neither overlooked nor treated in isolation. Full article

Primary humoral immunodeficiencies are a heterogeneous group of disorders defined by quantitative and/or functional defects in one or more immunoglobulin classes, often with associated cellular immune abnormalities. Their link with bronchiectasis, whose prevalence varies across specific defects, is largely driven by recurrent respiratory infections. Selective Immunoglobulin-(Ig)A deficiency and IgG2 subclass deficiency are the most frequent forms, but common variable immunodeficiency (CVID) is the condition most often associated with bronchiectasis and is usually diagnosed earlier because of its characteristic phenotype. In contrast, the contribution of isolated IgA deficiency or selective IgG subclass deficiencies to bronchiectasis remains controversial. Other reported associations include X-linked agammaglobulinemia, selective IgM or IgG deficiency, and rarer entities such as selective IgE deficiency, unclassified hypogammaglobulinemia, specific antibody deficiency, specific polysaccharide antibody deficiency, and heavy- or light-chain deficiencies. Current bronchiectasis guidelines recommend measurement of serum immunoglobulins and IgG subclasses in patients with compatible features, recurrent infections, or no clear etiology before labeling disease as idiopathic. Identifying immunoglobulin defects is clinically important because they represent treatable traits. The potential role of emerging therapies such as the DPP1 inhibitor brensocatib in immunodeficiency-related bronchiectasis remains uncertain, and ongoing registries will be key to clarifying these relationships. Full article

Background: Long-term non-invasive ventilation (LT-NIV) can prolong life expectancy and may reduce the number of exacerbations in patients with COPD. The eosinophilic phenotype has recently gained significant attention as a treatable trait in COPD. However, it is less known how this phenotype relates to exacerbations and mortality in patients who are set up on LT-NIV. Methods: A total of 191 patients with COPD (65 ± 8 years, 55% women) who were setup on LT-NIV and followed-up (28/15–49/months) at our tertiary centre were analysed. The eosinophilic phenotype was defined by using an accepted cutoff for blood eosinophil count (≥300 cells/µL). Results: A total of 37 patients had the eosinophilic phenotype (66 ± 9 years, 60% women). There was a higher reduction in the number of exacerbations (1.0/−1.0–3.2/ vs. 0.05/−1.4–1.63/, p < 0.01) and a trend for a reduction in the rate of hospitalisations (1.0/−1.0–2.0/ vs. 0.0/0.0–1.0/, p = 0.07) post-NIV setup in the eosinophilic group. Most importantly, patients with high eosinophil counts had longer overall survival (34/15–74/ vs. 28/15–47/ months, p = 0.02, adjusted for covariates). Conclusions: The eosinophilic COPD phenotype seems to show better clinical responses to long-term NIV than patients without this trait. Further mechanistic studies are warranted to analyse this association. Full article

Background: Interstitial lung diseases (ILDs) profoundly affect daily life, limiting mobility, independence, and emotional stability. While antifibrotic therapies may slow physiological decline, the living experience—characterized by breathlessness, cough, frailty, and psychological distress—remains insufficiently understood; this study therefore aimed to capture real-world patient perspectives on functional capacity, self-management, and mental health to identify treatable traits beyond conventional physiological measures. Materials and Methods: A cross-sectional quantitative online survey was conducted between September 2024 and January 2025 by Lungenfibrose e.V. in collaboration with the Center for Interstitial and Rare Lung Diseases (ZISL), Universities of Giessen and Marburg Lung Center (Giessen site). Patients with physician-confirmed ILD completed standardized instruments assessing dyspnea (MRC), cough intensity (VAS-Cough), frailty (CFS), and health-related quality of life (EQ-5D-5L). Data were analyzed descriptively across physical, functional, and psychosocial domains. Results: The majority of 69 respondents had idiopathic pulmonary fibrosis (64.7%) with a mean diagnostic delay of 1.4 ± 2.2 years; 69% were diagnosed within two years of symptom onset, and 77% were receiving antifibrotic therapy (nintedanib 57%, pirfenidone 19%). Functional limitations were substantial—55% were mobile for fewer than two hours per day, 73% reported mobility impairment, and oxygen use was common (51% during exertion, 26% at rest). Frailty increased over time (mean CFS 3.2 → 3.8), with 46% classified as fit, 36% vulnerable, and 18% frail. Dyspnea and cough remained burdensome (mean VAS-cough 40 ± 26; 58% moderate–severe), and health-related quality of life was reduced (mean EQ-VAS 56.5 ± 23.7), with high rates of anxiety/depression (78%), limitations in daily activities (76%), and pain/discomfort (74%). Despite overall satisfaction with care (mean 7.1 ± 2.5), respondents frequently reported unmet needs for psychological support and clearer communication about treatment and disease management. Conclusions: Despite antifibrotic therapy and structured specialist care, individuals living with ILD continue to face substantial physical and emotional challenges. Treatable traits—including frailty, dyspnea, inactivity, anxiety, and social isolation—emerge as key determinants of well-being. Multidisciplinary strategies integrating rehabilitation, psychosocial support, and patient education alongside pharmacological therapy are essential to preserve autonomy and improve quality of life in pulmonary fibrosis. Full article

Pediatric interstitial lung diseases (chILD) are a diverse and complex group of rare but impactful disorders characterized by heterogeneous etiologies and variable clinical courses. Traditional diagnosis-based management often delays targeted treatment, underscoring the need for a more precise therapeutic approach. The “treatable traits” framework, originally developed in adult respiratory medicine, offers a novel paradigm for personalized care by focusing on identifying and modifying discrete, clinically relevant features in each child. This narrative review synthesizes existing evidence and expert consensus to define key treatable traits in pediatric ILD, encompassing genetic and surfactant dysfunction, immune dysregulation, pulmonary hypertension, hypoxemia, aspiration, growth deficits, and environmental exposures. For each trait, we describe diagnostic pathways—including genetic testing, bronchoalveolar lavage, imaging, and functional assessments—and outline targeted management strategies. The implementation of a trait-based approach necessitates multidisciplinary collaboration, standardized protocols, and ongoing research to validate biomarkers and optimize therapies. By adopting this personalized strategy, clinicians can improve early diagnosis, tailor interventions, and potentially alter disease trajectories. Our discussion highlights the current limitations and future priorities, emphasizing the importance of pediatric-specific studies and international networks to fully realize the promise of precision medicine in pediatric ILD. Full article

Asthma management in children aims to prevent ongoing symptoms, preserve lung function and support normal daily activities. Impulse oscillometry (IOS) represents a modern approach to evaluating lung function that is also suitable for performing in the pediatric asthma population. Further research is warranted to clarify the role of IOS in the early identification of small airway disease (SAD) as a potential treatable asthma trait and to understand its implications for personalized treatment strategies. Before the integration of IOS into routine clinical protocols, it is necessary to establish population-specific reference values. Further studies in the pediatric population are needed to evaluate the added value of IOS in combination with conventional spirometry and fractional exhaled nitric oxide (FeNO). Future pediatric asthma management guidelines may consider incorporating the assessment of SAD with IOS as a possible tool for its evaluation. Full article