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BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.
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BACKGROUND: Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non-invasive biomarkers may facilitate diagnosis and treatment. Recently, Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammation in severe asthma, but also in such comorbidities as chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: The aim of this retrospective study was to evaluate the prevalence of SE-IgE sensitization in a multicentric Italian cohort of severe asthmatic patients and correlate it with demographic and clinical characteristics. RESULTS: A total of 249 patients were included in the analysis, out of which 25.3% were staphylococcal enterotoxin B (SEB)-IgE positive. We found a meaningful association between SEB-IgE and female gender, a positive association was also measured between CRS and CRSwNP. No significant association was found between SEB-IgE sensitization and atopy, the occurrence of exacerbations and corticosteroid dosages. In the SEB-IgE-positive patient, blood eosinophil count does not appear to be correlated with the severity of the disease. Patients with SEB-IgE sensitization are, on average, younger and with an earlier disease onset, thus confirming the possibility to consider SEB-IgE sensitization as an independent risk factor for developing asthma. CONCLUSIONS: Our data confirm that the search for SE in the initial screening phase of these patients is helpful to better phenotype them, may predict the evolution of comorbidities and lead to a targeted therapeutic choice; in this point of view this represents a goal of precision medicine.
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Asma , Pólipos Nasales , Femenino , Humanos , Staphylococcus aureus , Estudios Retrospectivos , Inmunoglobulina E , Enterotoxinas , Asma/diagnóstico , Asma/epidemiología , Gravedad del Paciente , Pólipos Nasales/epidemiologíaRESUMEN
BACKGROUND: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. OBJECTIVE: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. METHODS: One hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1 % predicted, nasal polyposis, bronchiectasis). RESULTS: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). CONCLUSIONS: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management.
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Antiasmáticos , Asma , Antiasmáticos/efectos adversos , Anticuerpos Monoclonales Humanizados , Asma/diagnóstico , Asma/tratamiento farmacológico , Análisis por Conglomerados , Progresión de la Enfermedad , Eosinófilos , Humanos , FenotipoRESUMEN
OBJECTIVE: Asthma is a frequent comorbidity of bronchiectasis, with possible implications for exacerbation and severity. We investigated the clinical impact of asthma on bronchiectasis in terms of disease severity and exacerbation risk. METHODS: We collected demographic, clinical, and functional characteristics of patients with a confirmed diagnosis of bronchiectasis. All patients were investigated for concomitant diagnosis of asthma. The Bhalla score was used to assess radiological severity of bronchiectasis, and the Bronchiectasis Severity Index (BSI) was used to assess the clinical severity. Blood and sputum samples were collected to assess blood cell count, erythrocyte sedimentation rate, c-reactive protein, immunological status (IgA, IgE, IgM, IgG, and IgG subclasses), and microbiological analysis. RESULTS: A total of 106 patients were enrolled in the study; 30.2% had concomitant asthma and were characterized by higher frequency of bronchiectasis exacerbation, despite higher Bhalla score and lower BSI compared to patients without asthma. Pseudomonas aeruginosa was more frequently isolated from the sputum of bronchiectasis patients without asthma. Total serum IgG, IgG1, and IgG3 were lower in patients with asthma. Blood eosinophils and exhaled nitric oxide were higher in patients with associated asthma. The presence of asthma and presence of Pseudomonas in sputum were the only significant determinants of frequent exacerbations in a binary logistic regression analysis. CONCLUSION: The coexistence of asthma and bronchiectasis is associated with an independent increase in the risk of bronchiectasis exacerbation despite lower radiological and clinical severity indexes. Asthmatic airway inflammation could promote an enhanced "Cole's Cycle" that is responsible for a higher frequency of exacerbations.
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Asma , Bronquiectasia , Asma/complicaciones , Asma/diagnóstico , Asma/epidemiología , Bronquiectasia/epidemiología , Eosinófilos/metabolismo , Humanos , Inmunoglobulina G , Índice de Severidad de la Enfermedad , Esputo/microbiologíaRESUMEN
OBJECTIVE: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences. METHODS: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844). RESULTS AND CONCLUSION: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease. ABBREVIATIONS: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting ß2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.
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Antiasmáticos , Asma , Administración por Inhalación , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/epidemiología , Estudios Transversales , Progresión de la Enfermedad , Humanos , Estudios Prospectivos , Calidad de VidaRESUMEN
Bronchiectasis (BE) is a long-term, chronic lung condition featured by widened and scarred airways. These can alter the physiological mucociliary clearance, making it difficult to clear mucus and microorganisms, leading to frequent exacerbations. High flow nasal therapy (HFNT) is a noninvasive respiratory support that delivers heated and humidified gas eventually enriched with oxygen, through a nasal cannula. Humidification is crucial for adequate airways mucociliary clearance, improving ciliary function and consequently reducing airways inflammation and recurrent infections. HFNT has been mostly used in patients with acute hypoxemic respiratory failure and in selected patients with chronic respiratory failure due to COPD. Still, evidence about its use in acute and long-term home setting in patients with clinically relevant BE are lacking. We report a case of severe widespread BE, already on top medical therapy and pulmonary rehabilitation, still suffering from difficult mucus expectoration and recurrent exacerbations, who has been additionally treated with HFNT, both in hospital and domiciliary, reporting significant improvements on relevant clinical and patient-centered outcomes. Thus, HFNT may confer additional benefits as an add-on treatment of patients with severe BE and respiratory failure.
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Acidosis Respiratoria , Bronquiectasia , Insuficiencia Respiratoria , Humanos , Terapia por Inhalación de Oxígeno , Bronquiectasia/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Oxígeno , Acidosis Respiratoria/etiologíaRESUMEN
BACKGROUND: Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. METHODS: A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016-2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). RESULTS: According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). CONCLUSIONS: There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.
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BACKGROUND: Anti-interleukin-5 (IL-5) monoclonal antibodies can be used as add-on biological therapies in allergic and non-allergic patients with severe eosinophilic asthma. However, within such a therapeutic context real-life investigations are lacking. OBJECTIVE: Therefore, the aim of the present observational study was to evaluate the effects of mepolizumab in allergic and non-allergic subjects with severe eosinophilic asthma. METHODS: Relevant clinical, functional, laboratory, and pharmacotherapeutic parameters were assessed in the above patient subgroups. RESULTS: After one year of add-on biological treatment with mepolizumab, our 88 patients experienced a remarkable improvement of their severe asthma, documented by a better symptom control, expressed by a significant improvement in asthma control test (ACT) score. Indeed, the mean value (±standard deviation) of ACT score increased from 12.55 (±3.724) to 21.08 (±3.358). Moreover, significant improvements were also detected with regard to the median values (interquartile range) of forced expiratory volume in one second (FEV1 ), blood eosinophil numbers, annual rate of disease exacerbations, and daily intake of oral corticosteroids (OCS). In particular, FEV1 enhanced from 1640 mL (1110-2275) to 1920 mL (1525-2615), blood eosinophil count dropped from 711.0 cells/µL (500.0-1022) to 90.00 cells/µL (50.00-117.5), the annual rate of asthma exacerbations decreased from 3.000 (2.000-6.000) to 0.000 (0.000-1.000), and the daily prednisone intake fell from 6.250 mg (0.000-25.00) to 0.000 mg (0.000-0.000). After one year of mepolizumab treatment, the improvements in clinical, functional, and haematological parameters were quite similar in patient subgroups characterized by skin prick test (SPT) negativity or positivity, respectively. A significant correlation was observed between serum IgE levels and OCS intake decrease (r = -0.2257; P < .05). CONCLUSION AND CLINICAL RELEVANCE: Hence, our real-life data suggest that mepolizumab can represent a valid add-on therapeutic option for patients with severe eosinophilic asthma, irrespective of IgE serum concentrations, and allergic sensitization.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Asma/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Asma/sangre , Asma/fisiopatología , Eosinofilia/sangre , Eosinofilia/tratamiento farmacológico , Eosinofilia/fisiopatología , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Índice de Severidad de la EnfermedadRESUMEN
The nonrecognition of asthma-associated comorbidities is often responsible for the therapeutic failure and the worsening of symptoms, and it is associated with frequent exacerbations, higher disease severity, and increased health costs. Bronchiectasis, one of the most frequent asthma-associated comorbidities, can increase airways inflammation and exacerbation rates and cause respiratory functional impairment. The aim of this article is to review the interactions between bronchiectasis and asthma, in order to better identify patients in the overlap between the 2 diseases and to select an "ad hoc" therapy. A literature search on PubMed/MEDLINE was performed using the following search terms: bronchiectasis in asthma, the association between asthma and bronchiectasis, comorbidities in asthma, and severe asthma. This review analyzed the following items: incorrect or underestimated diagnosis of asthma and bronchiectasis, prevalence of bronchiectasis in asthma, the impact of bronchiectasis in asthma, radiological imaging features of the 2 diseases, etiopathogenesis, and common causes (such as gastroesophageal reflux disease, immune deficits, chronic rhinosinusitis and allergic bronchopulmonary aspergillosis, and treatment of asthma and bronchiectasis). The concomitant presence of bronchiectasis and asthma should be suspected and investigated in patients with severe asthma, frequent exacerbations, and not responding to standard therapy. This clinical phenotype, characterized by a more severe disease, worse outcomes, and functional decline, must be readily recognized in order to choose the most appropriate therapeutic approach, able to potentially improve the management of bronchial asthma, to prevent the onset of exacerbations as well the functional decline, and to reduce health costs.
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Asma/complicaciones , Bronquiectasia/complicaciones , Asma/diagnóstico por imagen , Asma/terapia , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/epidemiología , Bronquiectasia/terapia , Humanos , Prevalencia , Radiografía TorácicaRESUMEN
The efficacy and feasibility of high flow nasal therapy (HFNT) use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and bronchiectasis is unknown. We performed a single-center, single-arm prospective observational study in patients with AECOPD, documented bronchiectasis, pH ≥ 7.35, respiratory rate (RR) ≥ 26 breaths/minute despite receiving maximal medical treatment and oxygen via face mask up to 10 L/m. Patients received HFNT (Airvo 2, Fisher & Paykel) at a gas flow of 50 L/min and FIO2 adjusted to maintain SpO2 ≥92%. Dyspnea, rated by Borg scale, RR, arterial blood gases and mucus production (ranging from 1 to 3) were collected before and 1 h after starting HFNT and then every 24 h for 3 days. Tolerance was measured using a visual analogic scale (VAS). Fifteen patients were enrolled. After 24 h, patients showed a significant improvement in dyspnea score [Borg scale from 6.7 ± 1.4 to 4.1 ± 1.3 (p<.001)]; RR decreased from 29.6 ± 2.7 breaths/min to 23.2 ± 2.9 breaths/min (p<.001); pCO2 significantly decreased after 24 h [58.4 ± 13 vs. 51.7 ± 8.2 (p=.003)] while quantity of mucus production increased [(1.1 ± 0,6 vs. 2.4 ± 0.7, p<.001)]. No patient received invasive or noninvasive mechanical ventilation. Overall VAS score for HFNT tolerance was 6.5. HFNT was effective in improving dyspnea score, decreasing RR, improving gas exchange, and increasing mucus production in patients with AECOPD and coexisting bronchiectasis. Moreover, no safety concerns on its use were detected. Nevertheless, due to the single-arm design, the effect of HFNT could not be isolated from standard pharmacological treatment due to the study design.
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Bronquiectasia/terapia , Terapia por Inhalación de Oxígeno/métodos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Anciano , Análisis de los Gases de la Sangre , Bronquiectasia/complicaciones , Bronquiectasia/fisiopatología , Cánula , Dióxido de Carbono/sangre , Disnea/etiología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Moco , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Frecuencia Respiratoria , Brote de los SíntomasRESUMEN
BACKGROUND: One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. OBJECTIVE: To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. METHODS: The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. RESULTS: A significant correlation between blood eosinophils assessed by the 2 devices was found (R2 = 0.854, P < .001); similar correlations were found also for white blood cells, neutrophils, and lymphocytes. The point-of-care device had the ability to predict blood eosinophil cutoffs used to select patients for biologic treatments for severe eosinophilic asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. CONCLUSION: The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management.
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Asma/sangre , Asma/diagnóstico , Eosinófilos , Recuento de Leucocitos , Sistemas de Atención de Punto , Adolescente , Adulto , Anciano , Asma/inmunología , Asma/terapia , Biomarcadores , Manejo de la Enfermedad , Eosinófilos/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Curva ROC , Reproducibilidad de los Resultados , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. OBJECTIVE: To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. METHODS: All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. RESULTS: Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono-sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. CONCLUSION: A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources.
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Anisakis/inmunología , Hipersensibilidad a los Alimentos/epidemiología , Alimentos Marinos/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alérgenos/inmunología , Animales , Antígenos Helmínticos/inmunología , Niño , Preescolar , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Sicilia/epidemiología , Pruebas Cutáneas , Adulto JovenRESUMEN
We herein present the case of a patient with frank hemoptysis and hematuria, dyspnea, and cough. The patient was known to be affected by Chronic Obstructive Pulmonary Disease (COPD) and dilated cardiomyopathy with atrial fibrillation. For this latter condition, he was supposed to take 1.25 mg warfarin daily. Laboratory findings revealed very high levels of International Normalized Ratio (INR) (16), and the patient referred that he self-increased warfarin dose to 5 mg daily since 8 days before the onset of symptoms. Computed tomography scan revealed diffuse bilateral signs of alveolar hemorrhage with hydroaerial levels within emphysematous cysts. Wafarin was immediately stopped and changed with 220 mg dabigatran daily, and he was properly treated to restore a normal coagulation status. We concluded for a case of diffuse alveolar hemorrhage because of warfarin overdose.
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Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Alveolos Pulmonares/efectos de los fármacos , Warfarina/efectos adversos , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Sobredosis de Droga , Disnea/etiología , Hematuria/inducido químicamente , Hemoptisis/inducido químicamente , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/patología , Warfarina/administración & dosificaciónRESUMEN
Treatment goals in asthma patients are the achievement of a good control of symptoms and the reduction of the risk of exacerbation. However, a "one-size-fits-all" therapeutic strategy is no longer appropriate to effectively pursue these goals, due to the heterogeneity of asthma. To make the treatment scenario even more complex, asthma patients often present comorbidities that may alter response to therapy. In addition, adherence to asthma treatment is poor. Given this complex and heterogeneous picture, the management of asthma is highly challenging. A clear diagnostic-therapeutic model of patients' care and the definition of the specific responsibilities of different healthcare providers appear necessary to improve clinical outcomes and better allocate healthcare resources. We present here a proposal for this model.
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Asma/diagnóstico , Manejo de la Enfermedad , Biomarcadores , Comorbilidad , Humanos , FenotipoRESUMEN
BACKGROUND: One of the main problem health care systems are facis is the mis-use and over-use of medical resources (including useless exams, surgical interventions, medical treatments, screening procedures ) which may lead to high health care related costs without increased patients' benefit and possible harm to the patients themselves. The "Choosing wisely" campaign, in Italy denominated "Doing more does not mean doing better", tries to educate doctors and citizens at a correct use of medical resources. METHODS: the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC) adhered to the "Doing more does not mean doing better" campaing and made a list of the 5 allergological procedures with the highest evidence of inappropriateness. RESULTS: the 5 recommendations were: "Do not perform allergy tests for drugs (including anhestetics) and/or foods when there are neither clinical history nor symptoms suggestive of hypersensitivity reactions"; "Do not perform the so-called "food intolerance tests" (apart from those which are validated for suspect celiac disease or lactose enzymatic intolerance)"; "Do not perform serological allergy tests (i.e.: total IgE, specific IgE, ISAC) as first-line tests or as "screening" assays"; "Do not treat patients sensitized to allergens or aptens if there is not a clear correlation between exposure to that specific allergen/apten and symptoms suggestive of allergic reaction"; "Do not diagnose asthma without having performed lung function tests". CONCLUSIONS: An important role scientific societies should play is to advise on correct diagnostic and therapeutical pathways. For this reason SIAAIC decided to adhere to the Slow Medicine Italy campaign "Doing more does not mean doing better" with the aim of warning the scientific community and the citizens/patients about some allergological procedures, which, when performed in the wrong clinical setting, may be not only useless, but unnecessarily expensive and even harmful for patients' health.
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Background: Bronchiectasis (BE) has been traditionally associated with neutrophilic inflammation, but eosinophilic bronchiectasis (EB) has recently emerged. Data about prevalence, clinical features, and disease severity are lacking. This study aimed to assess the EB prevalence, compare EB with non-EB, evaluate the Type-2 (T2) high endotype in BE (T2-high EB) versus non-T2-high EB, and identify EB predictors. Methods: We conducted a prospective study involving 153 BE patients. The data collected included clinical, radiological, and microbiological findings. BE severity was assessed using the bronchiectasis severity index (BSI), FACED and E-FACED scores, and the bronchiectasis etiology and comorbidity index (BACI). EB was defined as a blood eosinophil count (BEC) ≥ 300 cells/µL, and T2-high EB as BEC ≥ 300 cells/µL with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb. Results: Prevalence was 27% for EB and 20% for T2-high EB. EB patients exhibited poorer lung function and more severe radiologic features, with significantly higher severity scores [BSI, FACED, E-FACED, BACI (p < 0.05)], and a higher median exacerbation rate [4 (2-5) in EB vs. 2 (1-4) in non-EB, p = 0.0002], compared with non-EB patients. T2-high EB patients showed higher severity scores [BSI, FACED, E-FACED (p < 0.05)], as well as worse lung function parameters [FEV1%, FVC%, FEF 25-75% (p < 0.05)] compared with non-T2-high EB patients. In our study, patients with EB exhibited notably worsened lung function and higher BE severity scores compared with their non-EB counterparts, with exacerbations playing a major role in these differences. We found statistically significant positive correlations between BEC and disease severity scores, such as BSI, FACED, and mMRC, as well as an inverse relationship with pulmonary function. The likelihood of EB being present was significantly higher in association with mMRC ≥ 1 (OR = 2.53; 95% CI, 1.26-5.64), exacerbations/year ≥ 1 (OR = 1.27; 95% CI, 1.0-1.63), and chronic PA colonization (OR = 3.9; 95% CI, 1.08-15.8). Conclusions: EB is a distinct endotype. Dyspnea, exacerbations, and PA colonization may be predictive of EB, emphasizing the importance of early detection for improved outcomes. BEC could serve as a useful biomarker of disease severity to consider when diagnosing EB.
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BACKGROUND: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. OBJECTIVE: To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months. METHODS: The REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period. RESULTS: Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months, based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastro-esophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent. CONCLUSIONS: This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.
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Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease whose molecular pathogenesis remains unclear. In a recent paper, we demonstrated a key role for the PI3K pathway in both proliferation and differentiation into myofibroblasts of normal human lung fibroblasts treated with TGF-ß. In this research, we assessed the expression of class I PI3K p110 isoforms in IPF lung tissue as well as in tissue-derived fibroblast cell lines. Moreover, we investigated the in vitro effects of the selective inhibition of p110 isoforms on IPF fibroblast proliferation and fibrogenic activity. IHC was performed on normal and IPF lung tissue. Expression levels of PI3K p110 isoforms were evaluated by western blot and flow cytometry analysis. Fibroblast cell lines were established from both normal and IPF tissue and the effects of selective pharmacological inhibition as well as specific gene silencing by small interfering RNAs were studied in vitro. No significant differences between normal and IPF tissue/tissue-derived fibroblasts were observed for the expression of PI3K p110 α, ß and δ isoforms whereas p110γ was more greatly expressed in both IPF lung homogenates and ex vivo fibroblast cell lines. Myofibroblasts and bronchiolar basal cells in IPF lungs exhibited strong immunoreactivity for p110γ. Positive staining for the markers of proliferation proliferating cell nuclear antigen and cyclin D1 was also shown in cells of fibrolastic foci. Furthermore, both p110γ pharmacological inhibition and gene silencing were able to significantly inhibit proliferation rate as well as α-SMA expression in IPF fibroblasts. Our data suggest that PI3K p110γ isoform may have an important role in the etio-pathology of IPF and can be a specific pharmacological target.
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Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I/biosíntesis , Fibroblastos/enzimología , Fibrosis Pulmonar Idiopática/enzimología , Adulto , Procesos de Crecimiento Celular/fisiología , Células Cultivadas , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Colágeno/química , Ciclina D1/metabolismo , Femenino , Fibroblastos/citología , Silenciador del Gen , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Inmunohistoquímica , Pulmón/química , Pulmón/citología , Masculino , Persona de Mediana Edad , Miofibroblastos/citología , Miofibroblastos/enzimología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Isoformas de Proteínas , Inhibidores de Proteínas Quinasas/farmacología , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Thymosin ß4 (Tß4) was recently found at high concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with lung involvement. It has been hypothesized that Tß4 may exert a cyto-protective effect during lung injury because lower Tß4 levels were associated with interstitial lung disease progression. Moreover, Tß4 treatment prevented profibrotic gene expression in cardiac cells in vitro and in vivo. MATERIALS AND METHODS: In this study, we explored a putative Tß4 protective role in lung damage by utilizing a well-known in vivo model of lung fibrosis. C57BL/6 mice were treated with bleomycin (BLEO, 1 mg/kg) in the absence or presence of Tß4 (6 mg/kg delivered intraperitoneally on the day of BLEO treatment and for two additional doses). After sacrifice 1 week later, measurement of fluid and collagen content in the lung, BALF analysis, myeloperoxidase (MPO) activity assay, lung histology and IHC were performed. RESULTS: Compared with BLEO-treated mice, BLEO-treated mice who received Tß4 did not lose as much weight and had a higher survival rate. Moreover, BLEO-induced inflammation and lung damage were substantially reduced by Tß4 treatment, as demonstrated by the significant reduction in oedema, total collagen content, lung infiltration by leucocytes, MPO activity in lung homogenates, and histological evidence of the ongoing lung fibrosis. Results of IHC show a strong reactivity for Tß4 in the lung tissue of Tß4-treated mice. CONCLUSIONS: This is the first report that shows a Tß4 protective role in lung toxicity associated with BLEO in a mouse model. Future studies are needed to assess its putative antifibrotic properties.
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Antibióticos Antineoplásicos/toxicidad , Bleomicina/toxicidad , Lesión Pulmonar/prevención & control , Sustancias Protectoras/farmacología , Fibrosis Pulmonar/prevención & control , Timosina/farmacología , Animales , Líquido del Lavado Bronquioalveolar/citología , Colágeno/metabolismo , Modelos Animales de Enfermedad , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Peroxidasa/metabolismo , Edema Pulmonar/inducido químicamente , Edema Pulmonar/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Distribución Aleatoria , Timosina/metabolismo , Pérdida de PesoRESUMEN
Vitamin D deficiency is involved in the etiology of a broad range of diseases. Recently, some studies have shown a link between vitamin D and susceptibility to the onset of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic inflammation and irreversible airway obstruction. Systemic inflammation in COPD patients is associated with a decline in lung function. In addition, inflammation causes various extra-pulmonary symptoms, including muscle deterioration that leads to reduced strength and fatigue endurance, especially in muscles of the lower limb. In COPD the pathophysiological changes related to the inflammatory state affect oxidant-antioxidant balance, which is one of the main mechanisms promoting the progression of this disease and exacerbations. Vitamin D exerts beneficial effects and exhibits anti-inflammatory actions. Vitamin D deficiency in COPD patients affects inflammation, oxidative stress and mitochondrial impairment and can generate the development of skeletal atrophy. This systematic review offers a better understanding of the molecular mechanisms linking vitamin D deficiency to COPD and muscle weakness, and aims to establish whether vitamin D supplementation could be useful to mitigate inflammation in COPD patients.