INTRODUCTION:Timely initiation of biologic therapies is crucial in the management of severe asthma. However, delays in diagnosis and access to advanced treatments are common in real-life settings. We investigated disease progression and trajectories, with a focus on the impact of treatment latency among patients with severe asthma. METHODS:This longitudinal observational analysis included adult patients with severe asthma enrolled in the Italian Registry on Severe Asthma (IRSA). Data were stratified by use and timing of biologic therapy. Two core analyses were conducted: (1) characterization of patients not receiving biologics; (2) evaluation of disease progression and the relationship with the timing of biologic initiation. RESULTS:At baseline, 43.7% of the 2,114 patients were not receiving biologics, despite having severe disease and a T2-high phenotype. The average time of progression from initial diagnosis to severe asthma was 17 years. The median time from severe asthma diagnosis to biologic initiation was 2 years (IQR: 0.9-4.2). At the 1-year follow-up, patients who initiated biologics after enrollment showed the most significant clinical improvements compared with patients without biologic treatment or already on biologics at baseline, including a 64.8% reduction in the number of exacerbations (p = 0.019), a mean reduction in annual exacerbation rate of 4.1 events (p < 0.001), and an increase of 6.3 points in ACT score (p < 0.001). CONCLUSION:Severe asthma often develops after a prolonged progression from initial symptom onset. Structured referral and earlier biologic initiation may be associated with better outcomes and potentially influence the clinical trajectory of severe asthma.

Background Mild and moderate asthma are the most common forms of asthma, but they often remain poorly controlled due to inappropriate treatment strategies and low adherence. Formal consensus on best practices for managing mild-to-moderate asthma is still lacking. Objectives To achieve formal consensus on the management of mild-to-moderate asthma and validate the appropriateness and clinical feasibility of the recommendations in clinical practice. Methods A modified Delphi process involving a panel of respiratory experts was employed to formulate consensus statements across the following key domains identified through a cross-sectional survey administered to Italian allergists and immunologists: definition of asthma control, tools for assessment of asthma control, patient phenotyping, personalized treatment, and patient education and empowerment. The appropriateness and clinical feasibility of the agreed statements were validated with a RAND/UCLA method. Results Full consensus was reached on asthma control in mild-to-moderate asthma, defined as the absence of symptoms, exacerbations, limitation of daily activities, and the need for oral corticosteroids, together with the optimization of lung function. Assessment of control, future risk, and phenotype should be performed with appropriate tools and timing, to implement proactive management especially in patients at risk of exacerbations and disease progression. Conclusion This study provides a comprehensive, expert-driven consensus for the management of mild-to-moderate asthma, formally validated for appropriateness despite variability in real-world implementation. The findings support a patient-centric, proactive approach and offer practical recommendations to bridge the gap between guidelines and clinical practice.

Abstract Background Despite the availability of numerous guidelines for asthma management, their recommendations are not consistently implemented in clinical practice. This discrepancy between guidelines and real‐world practice among Italian healthcare professionals was explored during the “Revolution in Asthma” training program, which identified “gray areas” and barriers preventing clinicians from adopting guideline‐based approaches. Objective This study aims to analyze the key challenges in asthma management and provide evidence‐based solutions to improve adherence to guidelines in clinical practice. Methods A group of experts from the Scientific Committee of the Revolution in Asthma project reviewed the program's findings, focusing on three main areas of asthma management: diagnosis, control, and treatment. The experts summarized clinicians' main needs and questions for each area and provided evidence‐based responses and practical recommendations. Results The study highlights critical challenges in asthma treatment, addressing two key questions: (a) What are the possible uses and indications for short‐acting β‐agonists in asthma patients? (b) How should asthma treatment be initiated and adjusted based on asthma control? The expert panel developed practical, operational tools to support general practitioners and specialists (pulmonologists and allergists) in optimizing asthma management. Conclusion This paper serves as a knowledge co‐creation initiative, bridging the gap between clinical guidelines and daily practice. By offering concrete recommendations, it aims to enhance the application of guideline‐based asthma management among healthcare professionals.

In recent years, it was recognized that type-2 inflammation connects nasal polyposis and severe asthma (SA) in addition to other type-2 diseases. Thus, some biological drugs developed for SA appeared to exert a favourable effect also in nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies already used for SA were assessed also in chronic rhinosinusistis with nasal polyposis (CRSwNP), with promising results.Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT specialists, allergists, immunologists, pediatricians), it was felt that an updated educational and informative document was needed to better identify the indications of biological therapies in nasal polyposis. We collected the main Italian scientific societies, and prepared (under the umbrella of Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all societies, to provide a provisional statement for the future use of monoclonal antibodies (MAbs) as a medical treatment for polyposis, possibly associated with SA. The above mentioned document was the first endorsed document on this aspect, and the additional evidence required an update. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

Objective:Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma often coexist and share common underlying pathophysiological mechanisms. This study addresses challenges in the diagnosis and treatment of multimorbid patients with CRSwNP and asthma providing new insights for their management. Methods:Using a modified Delphi method, a scientific board of 40 Italian clinicians (pulmonologists, allergists/clinical immunologists, and ear, nose, and throat specialists) developed consensus statements regarding the multimorbid patient with severe CRSwNP and asthma and including the disease burden, assessment, treatment and multidisciplinary management of multimorbid patients. Results:All statements reached consensus. Experts acknowledged the substantial disease burden, the key pathophysiological role of type 2 inflammation in multimorbid patients and the need for multidisciplinary care. The use of biologics represents a highly effective therapeutic opportunity for patients with comorbidities, optimising overall outcomes. Integrated care pathways and regular multidisciplinary re-assessment were deemed essential for treatment decisions and improved care in multimorbid patients. Conclusions:This consensus highlights the value of a multidisciplinary approach for multimorbid CRSwNP and asthma patients, advocating for endotype-driven therapies and standardised pathways in clinical practice.

Summary:Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.

We treated 10 patients (mean age 58 years, 7 males) with severe eosinophilic asthma with dupilumab for 6 months. Patients at baseline had a mean peripheral blood eosinophil count of 460 103/uL. Total IgE 1154 IU/ml. Baseline FEV1 72% predicted on average, alveolar/capillary diffusion normal as well as 6mWT. Patients showed 5.3 mean exacerbations per year and 5/10 were steroid-dependent. Patients undergoing bronchoscopy with BAL and biopsies of bronchial mucosa. In all patients, we found evidence of moderate eosinophilic infiltrate involving the full-thickness bronchial mucosa. The search for infectious agents as well as auto-antibodies was negative. Baseline BAL: lymphocytes 14%, eos 0-1%. Baseline FENO 63 on average. Baseline ACT 9.7. After 6 months of therapy, patients improved clinically without presenting complications. ACT 22.6, FENO 23. Peripheral blood eosinophils were increased, mean 1,020 103/uL. Total igE passed to 832 IU/ml. FEV1 slightly increased at 79% predicted. Significant reduction in the number of exacerbations, equal to 1.1 on average. All patients discontinued the systemic steroid therapy. BAL after 6 months shows lymphocytes 12%, eos 0-1%. Bronchial biopsies: persistence of eosinophils in the bronchial mucosa in 7 out of 10 patients. Conclusions: 6-month treatment with dupilumab proved to be safe, effective on exacerbations and on steroid sparing. However, we show the persistence of eosinophils in the bronchial mucosa in patients under dupilumab. More studies are needed to confirm our data.

Abstract In this work, we investigate the correlation between ragweed pollen concentration and conjunctival, nasal, and asthma symptom severity in patients allergic to ragweed pollen using ambient pollen exposure in the Milan area during the 2014 ragweed season We calculate the pollen/symptom thresholds and we assess the effectiveness of ragweed allergen immunotherapy (AIT). A total of 66 participants allergic to ragweed (Amb a 1) were enrolled in the study and divided into two groups: AIT treated (24) and no AIT treated (42). Pollen counts and daily symptom/medication patient diaries were kept. Autoregressive distributed lag models were used to develop predictive models of daily symptoms and evaluate the short-term effects of temporal variations in pollen concentration on the onset of symptoms. We found significant correlations between ragweed pollen load and the intensity of symptoms for all three symptom categories, both in no AIT treated (τ = 0.341, 0.352, and 0.721; and ρ = 0.48, 0.432, and 0.881; p-value < 0.001) and in AIT treated patients ( $$\tau$$ τ = 0.46, 0.610, and 0.66; and ρ = 0.692, 0.805, and 0.824; p-value < 0.001). In both groups, we observed a positive correlation between the number of symptoms reported and drug use. Mean symptom levels were significantly higher in no AIT treated than in AIT treated patients (p-value < 0.001) for all symptom categories. Pollen concentration thresholds for the four symptom severity levels (low, medium–low, medium–high and high) were calculated. Ragweed pollen concentration is predictive of symptom severity in patients with a ragweed (Amb a 1) allergy. Patients treated with AIT had significantly reduced mean symptom levels compared to those without AIT.

BACKGROUND:Chronic cough (CC) is a burdensome health problem in adult and older people, with a major impact on quality of life. Its management is often troublesome, and many guidelines have been released. Notwithstanding, a proportion of cases still do not reach a definite diagnosis and resolutive treatment. A coordinated approach between different specialists would be highly recommended, but its implementation in clinical practice suffers from the lack of shared protocols and poor awareness of the problem. The present consensus document has been implemented to address these issues.AIMS:To develop evidence-based recommendations for the management of adults with CC.METHODS:A 12-member expert task force of general practitioners, geriatricians, pneumologists, allergologists, otorhynolaringologists and gastroenterologists was established to develop evidence-based recommendations for the diagnostic and therapeutic approach to subjects with CC. A modified Delphi approach was used to achieve consensus, and the US Preventive Services Task Force system was used to rate the strength of recommendations and the quality of evidence.RESULTS:A total of 56 recommendations were proposed, covering 28 topics and concerning definitions and epidemiology, pathogenesis and etiology, diagnostic and therapeutic approach along with the consideration of specific care settings.CONCLUSION:These recommendations should ease the management of subjects with CC by coordinating the expertise of different specialists. By providing a convenient list of topics of interest, they might assist in identifying unmet needs and research priorities.

Introduction: The Global Initiative for Asthma recommend Tiotropium (TIO) Respimat add-on therapy for patients with uncontrolled severe asthma (SA) (step5). Randomized double blinded studies showed that Tiotropium-Respimat added to high dose Inhaled Cortico-Steroids (ICS)/ Long-Acting β2-Agonists (LABA) treatment significantly improved lung function thus extending the time to the first asthma exacerbation and reducing frequency. Aim: To assess the use of triple inhaler therapy in Allergy and Pulmonology Departments adhering to the Italian Registry of Severe Asthma (IRSA). Methods: We analysed 1218 patients enrolled in the IRSA. All patients provided written informed consent. Results: 1215 patients (477 male, 738 female) were included in the analysis. 41% patients were treated with ICS/LABA/TIO and 59% with ICS/LABA. Patients taking Triple therapy had a worse lung function (FEV1 67%±21 vs 75%±20; p<0.001), high number of exacerbation/year (3.9±4 vs 2.8±3; p>0.001) and were regularly treated with systemic steroids (37% vs 28%). However, they had reduced IgE levels (520±1475 vs 561±1194). In addition, 57% of ICS/LABA/TIO patients used biologics compared to 66% of LABA/ICS patients. Conclusions: To reduce exacerbations, LABA/LAMA/ICS are recommended in patients with uncontrolled SA. Moreover, the optimization of inhaler therapy is mandatory before starting biological treatment approach. IRSA network revealed a low percentage of patients treated with triple combination therapy also in those using biologics. Additionally, IRSA Centres used to prescribe triple therapy especially to patients with more SA and a non-allergic phenotype.

Objectives: 1. To investigate the correlation between ragweed pollen concentration and conjunctival, nasal and asthma symptoms severity in patients allergic to ragweed using ambient pollen exposure in the Milan area during the 2014 ragweed season; 2. to calculate the pollen / symptom thresholds and 3. to assess the effectiveness of ragweed Allergen Immuno Therapy (AIT).Patients: 66 subjects allergic to Amb a 1 enrolled in the study and were divided into two cohorts: AIT treated (24) and non-AIT treated (42).Measurements: Pollen counts and daily symptom/medication patient diaries. Autoregressive Distributed Lag Models were used to develop predictive models of daily symptoms and to evaluate the short-term effects of temporal variations in pollen concentration on the onset of symptoms. Results: We found significant correlations between ragweed pollen load and the intensity of symptoms, for all three symptom categories respectively, both in non-AIT treated (𝛕= 0.341, 0.352, 0.721 and ρ = 0.48, 0.432, 0.881, p-value < 0.001) and in AIT treated patients (O= 0.46, 0.610, 0.66 and ρ = 0.692, 0.805, 0.824; p-value < 0.001). In both cohorts, we observed a positive correlation between the number of symptoms reported and drug use. Mean symptom levels were significantly greater in non-AIT treated than in AIT treated patients (p < 0.001) for all symptom categories. Pollen concentration thresholds for three symptom severity levels were calculated.Conclusions: Ragweed pollen concentration is predictive of symptom severity in ragweed (Amb a 1) allergy patients. AIT treated patients had significantly reduced mean symptom levels compared to non-AIT patients.

Introduction: Comorbidities in patients affected by severe asthma (SA) have different impact on asthma symptoms control. Moreover, prevalence rate of SA comorbidities are often increased by chronic Oral-Steroids (OCS) treatments. Aim: We evaluated the prevalence of comorbidities in patients enrolled in the Italian Registry of Severe Asthma (IRSA). Methods: 1218 patients were analysed and comorbidities were evaluated in four main treatments groups: (A) Long-Acting β2-Agonists+Inhaled-Cortico-Steroids (LABA+ICS), (B) LABA+ICS+other drugs, (C) LABA+ICS+Other drugs+Biologics, (D) OCS for over three months +Other drugs. Results: 1196 patients were analysed and one comorbidity affected 88% of subjects. Most common comorbidities were: sinusitis (52%), gastroesophageal reflux (GER) (44%), nasal polyposis (44%), hypertension (31%), obesity (20%), osteoporosis (20%), cataract (9%), diabetes (7%). Group D had more comorbidities with a prevalence of osteoporosis and cataract compared to other groups (D vs B and D vs C, p<0.001). Diabetes was common in Group B (8.5%) and D (8.4%). Obesity, GER and hypertension were equally distributed among Groups Conclusions: SA patients showed high comorbidities prevalence and reduced symptoms control. Moreover, chronic use of OCS strongly influences comorbidities rate. For those reasons, Biologics treatment optimization and OCS sparing interventions should be considered to reduce related comorbidities.

In the recent years, it was recognized that type-2 inflammation links many forms of nasal polyposis with severe asthma. Thus, some biological drugs developed for severe asthma appeared to exert an effect on nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies for severe asthma were assessed also in polyposis, with promising results. Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT, allergists), it was felt that an educational and informative document was needed to better identify the indications of biologicals in nasal polyposis. We collected the main Italian Scientific Societies, and prepared (under the Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all Societies, to provide a provisional statement for the future use of monoclonal antibodies as a medical treatment for polyposis. It is the first nationwide endorsed document on this aspect. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

Introduction: Severe Asthma (SA) affects 5% of the asthma population and patients have frequent exacerbations and inadequate asthma control although appropriate treatment. Biological therapies represent a major advancement in the management of SA however, due to the heterogeneity of clinical outcomes and phenotypes the use of specific biomarkers is pivotal to identify the most effective treatment. Aim: We evaluated how Italian Allergists and Pulmonologists approach SA patients and manage biomarkers for asthma phenotyping and the identification of the most appropriate treatment. Methods: AAIITO and AIPO-ITS submitted a multiple choice survey questions to Allergy and Pulmonology Departments adhering to the Italian Registry of Severe Asthma. Results: The 87.85% of Centers used biomarkers in clinical practice considering useful in the diagnosis of SA (99.07%). Blood eosinophils count (97.78%), total serum IgE (85.56%) and exhaled Nitric Oxide (72.22%) are the most used. High IgE are related to uncontrolled atopic asthma phenotype, with a positivity to perennial allergens, potentially treatable with Omalizumab. On the contrary, high levels of blood eosinophils identified a phenotype suitable for treatment with Mepolizumab. Low values of eosinophils and IgE characterized patients who could benefit from thermoplastics. Periostin and IL5 are considered possible future effective biomarkers. Centers declared to manage 35 SA patients/Center and to be authorized for monoclonal antibodies therapies (84.5%). Conclusions: A close collaboration between Allergists and Pulmonologists is pivotal to recognize the importance of biomarkers in the diagnosis, phenotyping and monitoring of SA.

Rheumatoid arthritis (RA) can affect the lung, with different types of involvement: sometimes a radiological fibrotic pattern such as Usual Interstitial Pneumoniae (UIP) can develop. Chest CT scan is completely indistinguishable from that of idiopathic pulmonary fibrosis (IPF), with honeycombing and traction bronchiectasis, although some reports seem to show that pulmonary fibrosis cysts of RA patients are larger than those of IPF patients. In RA patients with UIP pattern (connective-tissue-disease/interstitial-lung-disease, CTD-ILD), studies show a severe prognosis in the medium term, only slightly better than the idiopathic form of fibrotic pulmonary involvement. We assessed the clinical and functional trend of patients with CTD-ILD due to RA treated with Rituximab in our center. We reached 5 years of follow up. We have enrolled 26 patients. Multidisciplinary group diagnosis was made. Patients received Rituximab therapy, 1,000 mg for 2 administrations. The patients showed only 1 episode of complication, an immune complex reaction at the level of the shoulder girdle, which resolved itself and which did not prevent a second treatment. Conclusions: Rituximab has been shown to be safe with only one mild adverse reaction episode. Breath tests show stability with tendency to improve until 3 years and a slight reduction after it. We are still studying the cohort.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by exposure to organic antigens that cause an immune response mediated by T lymphocytes in susceptible subjects. There is an acute/subacute variant and a chronic variant characterized by fibrotic evolution (cHP). We evaluated functional progression in cHP patients, with a monocentric retrospective observational study. We enrolled 66 patients (14 woman) with an average age at diagnosis of 69 years with a median follow up of 56 months. Diagnosis has been made through multidisciplinary evaluation. Hospitalizations for respiratory causes was 1.6 times per patient. Of the 66 patients, 16 died, 4.2 years after diagnosis. Bronchoscopy: on average, BAL at Neutrophils 8.01%, Lymphocytes 22.02%, Macrophages 64.39%, Eosinophils 2.05%, Basophils 0.00%, and a CD4 / CD8 ratio of 1.53. Chest CT scan: the prevalent lesion in patients was honeycombing (59/66), followed by micronodules (45/66), air trapping (44/66) and traction bronchiectasis (34/66). cHP represents a severe disease, with poor prognosis that can worse in the short/medium term from diagnosis.

Rheumatoid arthritis (RA) during its natural history can affect the lung. Pulmonary involvement is variable: sometimes a radiological fibrotic pattern such as Usual Interstitial Pneumoniae (UIP) can develop. Chest CT scan is completely indistinguishable from that of idiopathic pulmonary fibrosis (IPF), with honeycombing and traction bronchiectasis, although some reports seem to show that pulmonary fibrosis cysts of RA patients are larger than those of IPF patients. In RA patients with UIP pattern (connective-tissue-disease/interstitial-lung-disease, CTD-ILD), studies show a severe prognosis in the medium term, only slightly better than the idiopathic form of fibrotic pulmonary involvement. We assessed the clinical and functional trend of patients with CTD-ILD due to RA treated with Rituximab in our center. In the past 3 years we have enrolled 23 patients. Multidisciplinary group diagnosis was made. Patients received Rituximab therapy, 1,000 mg for 2 administrations. In the table are summarized the risults obtained in these 3 years. The patients showed only 1 episode of complication, an immune complex reaction at the level of the shoulder girdle, which resolved itself and which did not prevent a second treatment. Conclusions: Rituximab has been shown to be safe with only one mild adverse reaction episode. Breath tests show stability of the picture with a slight tendency to improve. We look forward to completing the 3-year follow up.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by exposure to organic antigens that cause an immune response mediated by T lymphocytes in susceptible subjects. There is an acute/sub-acute variant and a chronic variant characterized by fibrotic evolution (cHP). We evaluated functional progression in cHP patients, with a monocentric retrospective observational study. We enrolled 54 patients, average age at diagnosis: 68 , 12 women. Average follow up: 44 months. Diagnosis made through multidisciplinary evaluation. The number of average hospitalizations for respiratory causes was 1.6 per patient. Of the 54 patients, 9 died, 4.1 years after diagnosis. Bronchoscopy: on average, BAL at Neutrophils 7.89%, Lymphocytes 21.26%, Macrophages 66.19%, Eosinophils 1.15%, Basophils 0.00%, and a CD4 / CD8 ratio of 1.49. Chest CT scan: the prevalent lesion in patients was honeycombing (48/54), followed by micronodules (37/54), air trapping (36/54) and traction bronchiectasis (28/54). cHP represents a severe disease, with a prognosis that can become poor in the short/medium term from diagnosis. These are preliminary data.