RESUMO
Purpose: This article illustrates the replication of asthma and COPD conditions in a laboratory setting and the potential applications of this methodology.Introduction: Biologic drugs have been shown to enhance the treatment of severe asthma and COPD. Monoclonal antibodies against specific targets have dramatically changed the management of these conditions. Although the inflammatory pathways of asthma and COPD have already been clearly outlined, alternative mechanisms of action remain mostly unexplored. They could provide additional insights into these diseases and their clinical management.Aims: In vivo or in vitro models have thus been developed to test alternative hypotheses. This study describes sophisticated ex vivo models that mimic the response of human respiratory mucosa to disease triggers, aiming to narrow the gap between laboratory studies and clinical practice.Results: These models successfully replicate crucial aspects of these diseases, such as inflammatory cell presence, cytokine production, and changes in tissue structure, offering a dynamic platform for investigating disease processes and evaluating potential treatments, such as monoclonal antibodies. The proposed models have the potential to enhance personalized medicine approaches and patient-specific treatments, helping to advance the understanding and management of respiratory diseases.
RESUMO
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.
RESUMO
INTRODUCTION AND OBJECTIVES: Chronic respiratory diseases are associated with an increased risk of cardiovascular diseases (CVD); however, it is unknown whether some respiratory diseases are at higher risk than others. In this perspective, head-to-head studies comparing bronchiectasis and chronic obstructive pulmonary disease (COPD) are encouraged. We explored whether the prevalence of cardiovascular risk factors (diabetes mellitus and hyperlipidemia) and cardiovascular comorbidity (systemic hypertension, ischemic heart diseases, cardiac arrhythmia, stroke) are different in these two diseases. METHODS: The present retrospective case-control study aimed to compare patients with bronchiectasis with age and sex-matched individuals with COPD. A total of 63 patients with bronchiectasis and 63 with COPD were retained for analysis. RESULTS: Patients with bronchiectasis had a lower risk of systemic hypertension (OR 0.42 (C.I. 0.20 to 0.87)) and diabetes mellitus (OR 0.28 (C.I. 0.09 to 0.81)). In contrast, ischemic heart diseases, cardiac arrhythmia, stroke, and hyperlipidemia did not differ between the two groups. Logistic regression analysis showed that age, male sex, and COPD remain independent risk factors for having at least one condition of a composite index including the above-mentioned CVD and CV risk factors. In detail, a patient with COPD has a risk of 4.648 times (C.I. 1.48 to 15.78) for having at least one CVD compared with a patient with bronchiectasis. CONCLUSIONS: The current findings suggest that subjects with bronchiectasis may experience lower cardiovascular risk than those with COPD. Larger studies are needed to confirm this preliminary observation and its clinical implications.
RESUMO
RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.
RESUMO
OBJECTIVE: Nocturnal symptoms are common in the asthmatic population, reflecting an exaggerated airway narrowing overnight due to several factors; it is questioned to what extent the awakenings documented in the clinical assessment of asthma control are due to the disease itself or to comorbidities. To answer this question, we aimed to evaluate to what proportion rhinitis, gastroesophageal reflux and the likelihood of being affected by OSAS were related to poor asthma control, by means of ACT evaluation. METHODS: Asthmatics attending the outpatient clinic were enrolled and administered the following questionnaires: ACT, Total 5 Symptom Score, GERD Impact Scale, Pittsburgh Sleep Quality Index and the Sleep Disorders Questionnaire. RESULTS: One-hundred consecutive patients (M/F: 42/58, mean age 52 ± 15 years) were recruited. According to the ACT findings, 14 asthmatics resulted as fully controlled (FC, ACT equal to 25), 55 partially controlled (PC, 25 < ACT >19) and 31 as uncontrolled (UC, ACT <19). GERD was not associated with the ACT score neither did rhinitic symptomatology. On the other hand, the PSQI scores appeared to significantly increase with the lack of symptom control: FC, 2.0 (1-4); PC, 3.5 (2-5); UC, 6.6 (4-8) (p = 0.002). The SA-SDQ questionnaire results significantly increased with the loss of asthma control: FC, 11.0 (9-12); PC, 12.5 (10-14); UC, 15.1 (14-16) (p = 0.005). CONCLUSIONS: These results confirm and extend previous findings showing that there is a higher likelihood that underlying unknown sleep disturbances worsen asthma control, suggesting that a more comprehensive assessment is necessary to clarify the cause of nocturnal symptoms in asthma.
Assuntos
Asma , Comorbidade , Refluxo Gastroesofágico , Humanos , Asma/epidemiologia , Asma/fisiopatologia , Asma/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/fisiopatologia , Adulto , Idoso , Inquéritos e Questionários , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Rinite/epidemiologia , Transtornos do Sono-Vigília/epidemiologiaRESUMO
Despite the worldwide recommendations for influenza immunisation, vaccination coverage for patients exposed to the highest risk of severe complications is still far from the optimal target. The need to take advantage of alternative methods to provide vaccination is essential. This study presents a hospital-based strategy which offers influenza vaccination to inpatients at discharge. This study was conducted during the 2022-2023 influenza season at the University Hospital of Palermo. A questionnaire was administered to identify the determinants for the acceptance of influenza vaccination in the frail population. Overall, 248 hospitalised patients were enrolled, of which 56.1% were female and 52.0% were over 65 years of age. The proportion of patients vaccinated against influenza during hospitalisation was 62.5%, an increase of 16% in influenza vaccination uptake among frail people in comparison with the previous influenza season (46.8% vaccinated during the 2021-22 influenza season). Factors significantly associated with vaccination acceptance were the following: to have received influenza vaccine advice from hospital healthcare workers (OR = 3.57, p = 0.001), to have been previously vaccinated for influenza (OR = 3.16 p = 0.005), and to have had a low level of education (OR = 3.56, p = 0.014). This study showed that offering influenza vaccination to hospitalised patients could be an effective strategy to increase vaccination coverage in the most vulnerable population, and these findings could be useful for planning and improving future influenza vaccination campaigns.
RESUMO
Background: The current definition of severe eosinophilic asthma (SEA) super-responders to biologic treatment does not include patients with other eosinophil-based comorbidities. Although eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with SEA, we lack data on a possible super-response to biologic treatments in patients suffering from these two diseases. We aim to assess super-responder features in real-life patients with SEA and EGPA treated with mepolizumab and benralizumab. Methods: We enrolled 39 patients with SEA and EGPA eligible for treatment with mepolizumab or benralizumab. Super-responder assessment was performed considering oral corticosteroid (OCS) cessation, lack of exacerbations, forced expiratory volume in 1â s and Asthma Control Test (ACT) improvement. Results: Super-responders showed worse clinical baseline characteristics than non-super-responder patients, with a greater improvement in severe asthma exacerbations, OCS dose reduction and ACT score increase. Definition of super-responders was consistent only considering a 12-month course of monoclonal antibody, lacking sensitivity in earlier evaluations. Conclusion: Mepolizumab and benralizumab are safe and effective in patients with EGPA and SEA, since a consistent proportion of patients show a super-response after 12â months of treatment. Further studies will address specific criteria for super-responder assessment in these patients.
RESUMO
Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia. Objective: To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months. Methods: We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed. Results: 49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p<0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab (p<0.0001), while benralizumab depleted both eosinophils (p<0.0001) and basophils (p<0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients. Conclusions: These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.
Assuntos
Asma , Produtos Biológicos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Humanos , Granulomatose com Poliangiite/tratamento farmacológico , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Imunossupressores/uso terapêutico , Asma/tratamento farmacológicoRESUMO
INTRODUCTION: Asthma is commonly considered a disease of younger ages; however, it is not infrequent to pose a diagnosis of the disease in older individuals. Although current recommendations do not distinguish between young and old asthmatics in terms of diagnostic and therapeutic approaches, asthma in the elderly may present with peculiar features that contribute to complicate its management. AREAS COVERED: The current review focuses on the challenges that arise when approaching an older individual with suspected asthma. Age-associated changes of the lung may complicate the diagnostic approach. Measurement of the forced expiratory volume in the first 6 s (FEV6) in an easier and faster alternative to FVC estimation, and residual volume should always be assessed. Older individuals are often affected by concomitant diseases, both age- and drug-related, that need to be considered when approaching elderly asthmatics, since they can affect the efficacy of the treatment as well as the control of the disease. EXPERT OPINION: The potential drug to drug interaction should be routinely investigated, and documented in medical records. The effect of aging on the response to pharmacological therapy in older asthmatics should be explored. Therefore, the need of a multidisciplinary and multidimensional approach to the elderly asthmatics is strongly encouraged.
Assuntos
Asma , Humanos , Idoso , Asma/diagnóstico , Asma/tratamento farmacológico , Envelhecimento , Pulmão , Testes de Função Respiratória , Volume Expiratório Forçado/fisiologiaRESUMO
Background: The efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation. Objective: To assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence. Methods: Clinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP. Results: Among the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01). Conclusion: Our results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation.
Assuntos
Asma , Hipersensibilidade Imediata , Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/complicações , Rinite/tratamento farmacológico , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Inflamação , Sinusite/complicações , Sinusite/tratamento farmacológico , Asma/complicações , Asma/diagnóstico , Asma/tratamento farmacológico , Doença CrônicaRESUMO
PURPOSE OF REVIEW: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the most severe forms of asthma has been an object of discussion. Indeed, it is not clear whether asthma is among the risk factors for the occurrence of severe coronavirus disease 2019 (COVID-19) disease, or rather it plays a protective role against the worsening of the respiratory involvement in the SARS-CoV-2 infection. On the other hand, the extent to which coronavirus infection may trigger asthma attacks is still partly unknown. The current investigation aims at reviewing the available literature on the topic to address factors influencing this relationship. RECENT FINDINGS: Based on recent observations, it is likely that type 2 inflammation plays a protective role against SARS-CoV-2 infection and disease. In particular, asthmatics show different expression of angiotensin-converting enzyme2 (ACE2) and Transmembrane protease, serine 2 (TMPRSS2) that are responsible for a reduced risk of infection as well as lower risk of hospitalization. Interestingly, studies showed a safe profile of inhaled corticosteroids and biological drugs in SARS-CoV-2 infection. In addition, inhaled corticosteroid could play a protective role against worsening of asthma. SUMMARY: The current findings suggest that current treatment for asthma should be maintained to avoid severe exacerbations. Severe asthmatics under biological treatment should continue their medications, and be encouraged to receive COVID-19 vaccines.
Assuntos
Asma , COVID-19 , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Peptidil Dipeptidase A/metabolismoRESUMO
BACKGROUND: COVID-19 is an infectious disease caused by a Coronavirus in humans, namely SARS-CoV-2, which has quickly become a global pandemic. The infection is responsible for a severe form of pneumonia, which may lead to lung failure and death. Among the therapeutic strategies, the antiviral agent remdesivir has become one of the most used drugs. The current literature reports a causal correlation between remdesivir administration and the incidence of cardiovascular effects. We aimed to further investigate this relationship, by exploring the association between the use of remdesivir and the onset of bradyarrhythmic disorders. METHODS: We reviewed medical records, blood exams and chest imaging of 85 patients with COVID-19 pneumonia (M/F: 57/28, age: 61±12 years) admitted between September 2020 and May 2021 to the Division of Respiratory Diseases in Palermo, Italy. RESULTS: We found a significant correlation between treatment with remdesivir and the occurrence of bradycardia, lasting for at least 3 days, which returned to normal values after the discontinuation of the drug. A significant reduction in heart rate (HR) was observed in the days following remdesivir administration (L. ratio 47.4, P<0.0001) in 24 patients (HR on the first day of observation: 75±14 bpm; at discharge: 72±14 bpm). Cardiac events occurred more frequently in subjects with extensive pulmonary involvement (greater than 50% of the total parenchyma, as assessed by chest CT). CONCLUSIONS: We suggest to carefully monitor the administration of the drug in patients with risk factors for arrhythmic or cardiovascular events.
Assuntos
COVID-19 , Humanos , Pessoa de Meia-Idade , Idoso , SARS-CoV-2 , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Bradicardia/tratamento farmacológico , Tratamento Farmacológico da COVID-19 , Antivirais/efeitos adversosRESUMO
The "Blood pressure levels, clinical features and markers of subclinical cardiovascular Damage of Asthma patients" (BADA) study is aimed at defining the cardiovascular risk profile and the markers of subclinical and clinical vascular and cardiac damage in asthmatic patients. Very few studies have assessed asthmatic patients without concomitant heart disease through a transthoracic echocardiogram. The goal of the present study is to investigate the prevalence of morphology and/or function changes in the cardiac chambers of a sample of 86 patients with chronic asthma, referred to the dedicated outpatient unit of the Division of Respiratory Diseases of the AOUP "P. Giaccone" of the University of Palermo, and the results obtained were compared with those of a control group without respiratory or cardiovascular diseases. Patients with asthma showed a marked and widespread involvement of the four cardiac chambers compared with the controls: enlargement of the two atria, greater left ventricular remodeling with interventricular septal thickening, increased indexed left ventricular mass with a significantly greater percentage of patients with overt left ventricular hypertrophy, worse left ventricular diastolic function proven by the significant difference in the E/A ratio, and worse right ventricular systolic function with global right ventricular dysfunction estimated by the Myocardial Performance Index (Tei Index). Multivariate regression analysis, after adjustment for essential hypertension, hypertension severity, diabetes, Body Mass Index, and creatinine clearance, seems to indicate that the indexed left ventricular mass, right atrial volume, and right ventricular Tei index (but not left ventricular hypertrophy) correlate significantly with asthma, severe asthma, and FEV1 (and to a lesser extent with asthma duration). No correlation is apparent between inhaled therapy (ICS, SABA) and myocardial involvement. These results seem to confirm that a more in-depth cardiovascular evaluation in patients with chronic respiratory disease allows the identification of unrecognized cardiovascular involvement. A transthoracic echocardiogram performed in asthmatic patients without clinically overt signs or symptoms of cardiovascular impairment has identified some features indicative of an early subclinical cardiac impairment not found in the control group. These findings, considering also the higher frequency of hypertension in the asthma group, deserve further validation in the future.
RESUMO
MASK-air®, a good practice of the DG Santé, has been fully validated in allergic rhinitis, but little is known about its applicability to asthmatics. We explored whether the MASK-air® application is applicable to patients with severe asthma. Severe asthmatics were proposed to use the MASK-air® application for 6 months, along with best practice treatment. Treatment of the patients was not changed based on the application results. The evolution of the visual analogue scales (VAS) for asthma, shortness of breath, rhinitis, conjunctivitis, work, and sleep was monitored using MASK-air®. Adherence to MASK-air® and to the asthma treatment was also checked. Thirteen patients reported on 1229 days of MASK-air® use. The average application adherence was 51.8% (range: 19.7-98.9%). There was no correlation between application and medication adherence. Highly variably trends were found for the VAS for asthma. Five patients had over 90% well-controlled days, four had well- or moderately controlled asthma (with up to 20% uncontrolled days), one patient had moderately controlled asthma with approximately 20% uncontrolled days, and one patient had 80% uncontrolled days. Highly significant correlations were found for the VAS for asthma, and other patients reported VASs for work, dyspnea, sleep, and rhinitis. MASK-air® can be used in patients with severe asthma. VAS asthma appears to be an interesting patient-reported outcome highly correlated with dyspnea and impacts on work. Adherence to the application was better than that for rhinitis, but it needs to be improved.
Assuntos
Asma , Produtos Biológicos , Aplicativos Móveis , Rinite Alérgica , Rinite , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Dispneia , Humanos , Projetos Piloto , Rinite Alérgica/tratamento farmacológicoRESUMO
COVID-19 modified the healthcare system. Nasal-pharyngeal swab (NPS), with real-time reverse transcriptase-polymerase (PCR), is the gold standard for the diagnosis; however, there are difficulties related to the procedure that may postpone it. The study aims to evaluate whether other elements than the PCR-NPS are reliable and confirm the diagnosis of COVID-19. This is a cross-sectional study on data from the Lung Unit of Pavia (confirmed) and at the Emergency Unit of Palermo (suspected). COVID-19 was confirmed by positive NPS, suspected tested negative. We compared clinical, laboratory and radiological variables and performed Logistic regression to estimate which variables increased the risk of COVID-19. The derived ROC-AUCcurve, assessed the accuracy of the model to distinguish between COVID-19 suspected and confirmed. We selected 50 confirmed and 103 suspected cases. High Reactive C-Protein (OR: 1.02; CI95%: 0.11-1.02), suggestive CT-images (OR: 11.43; CI95%: 3.01-43.3), dyspnea (OR: 10.48; CI95%: 2.08-52.7) and respiratory failure (OR: 5.84; CI95%: 1.73-19.75) increased the risk of COVID-19, whereas pleural effusion decreased the risk (OR: 0.15; CI95%: 0.04-0.63). ROC confirmed the discriminative role of these variables between suspected and confirmed COVID-19 (AUC 0.91). Clinical, laboratory and imaging features predict the diagnosis of COVID-19, independently from the NPS result.
RESUMO
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.
Assuntos
Antiasmáticos , Asma , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados , Asma/diagnóstico , Asma/tratamento farmacológico , Análise por Conglomerados , Progressão da Doença , Eosinófilos , Humanos , FenótipoRESUMO
SARS-CoV-2 pandemic has contributed to implement telemedicine, allowing clinicians to follow the patient remotely, therefore minimizing the risk of any exposure to positive COVID-19 patients. We summarize the approaches adopted to treat and monitor severe asthmatic patients during the lockdown phase of the pandemic. Our experience supports the strategy that every effort should be made to minimize patient contact with the health-care system, planning a pathway that allows patients to receive appropriate medical care and continue the biological therapies, thus preventing the loss of disease control and acute severe exacerbations.
Assuntos
Asma , COVID-19 , Asma/epidemiologia , Asma/terapia , Controle de Doenças Transmissíveis , Humanos , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
OBJECTIVE: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking. METHODS: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic. RESULTS: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic. CONCLUSIONS: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.
Assuntos
Antiasmáticos/uso terapêutico , Asma/dietoterapia , Asma/epidemiologia , COVID-19/epidemiologia , Antiasmáticos/administração & dosagem , Humanos , Pandemias , Gravidade do Paciente , Guias de Prática Clínica como Assunto , Fatores de Risco , SARS-CoV-2RESUMO
OBJECTIVE: Management of asthma includes monitoring of inhaler technique and level of adherence to treatment. Both factors could be influenced by high frequency of switching inhaler devices. We explored whether switching inhalers is an independent predictive factor of exacerbations. METHODS: Data were collected from 2015 to 2017 from the outpatient clinic of asthma at the University of Palermo, Italy. This observational study consisted of two phases: Phase 1 included subjects of at least three visits in the previous year who reported the frequency of inhalers switched; Phase 2 included subjects of at least two visits during the second year, and the rate of switches and exacerbations was recorded. We included adult (24-84 years old) mild/moderate asthmatics under regular inhaled treatment; uncontrolled asthma was defined as poor symptom control, exacerbations (≥2/year) requiring oral corticosteroids (OCS), or serious exacerbations (≥1/year) requiring hospitalization. RESULTS: A total of 109 records were retrieved for the analysis. A significant correlation between the rate of switches in Phase 1 and exacerbations in Phase 2 was found (p = 0.001). Age and the rates of exacerbations in Phase 1 were also independently associated with a higher number of exacerbations in Phase 2 (p < 0.0001). The multivariate regression model showed that the numbers of switches, as well as exacerbations in Phase 1, were independently correlated to the number of exacerbations in Phase 2 (p = 0.003). CONCLUSIONS: The frequency of switching inhalers independently affects the risk of exacerbations in asthma. These results imply that changing inhaler requires careful management in clinical practice.
Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Hospitalização , Humanos , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Adulto JovemRESUMO
Surfactant decreases the surface tension of peripheral airways and modulates the immunological responses of the lung. The alterations of surfactant due to the airway inflammation suggest a role in the pathogenesis of asthma. We aim to test the hypothesis that serum levels of SP-A (Surfactant Protein A) and SP-D (Surfactant Protein-D) are altered in patients with mild asthma compared to healthy controls and those alterations are related to functional abnormalities of peripheral airways, which are an early marker of progression of asthma. In this pilot study, we recruited 20 mild asthmatics and 10 healthy controls. We measured serum SP-A and SP-D and all subjects underwent clinical, lung functional and biological assessments. Serum SP-D was significantly higher in asthmatics compared to healthy controls (mean (SD) values: 7.9(4.65) vs 3.31(1.71) ng ml-1,p-value: 0.008). In the asthmatic group, serum SP-D was significantly correlated to CalvNO (alveolar NO concentration) (R-squared: 0.26;p-value: 0.014). These preliminary findings suggest that serum SP-D could be used as a lung-specific biomarker of small airways damage thus predicting the progression to the most severe forms of asthma.