Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

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.

Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission.

Introduction: Clinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria. Methods: We enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission. Results: 30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV1% between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement. Discussion: anti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items.

Real-world characteristics of "super-responders" to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis.

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 1 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 12 months of treatment. Further studies will address specific criteria for super-responder assessment in these patients.

Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study.

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.

Characteristics of severe asthma patients on biologics: a real-life European registry study.

Background: The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs. Materials and methods: We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies. Results: Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids. Conclusion: A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.

Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps.

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.

The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy.

BACKGROUND: There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. OBJECTIVE: This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. METHODS: An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. RESULTS: Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. CONCLUSIONS: Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.

Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study.

INTRODUCTION: Asthma and bronchiectasis appear to be two related diseases and in their complex inflammatory interaction, the cysteinyl leukotriene/cysteinyl leukotriene receptor 1 (cysLT/cysLTR1) axis appears to play an important role given its involvement also in the neutrophilic pathway. To our knowledge, few studies have been conducted so far to evaluate the role of the leukotriene cysLT/cysLTr1 axis in the management of clinical and inflammatory outcomes within a population of patients with severe asthma and bronchiectasis. The aim of our study was to verify in this population the effect of leukotriene receptor antagonist (LTRA) therapy in clinical and inflammatory control before and after 6 months of introduction of biologic therapy. METHODS: We retrospectively enrolled, from eight different severe asthma centers' outpatients, 36 atopic patients with the simultaneous presence of non-cystic fibrosis (non-CF) and non-allergic bronchopulmonary aspergillosis (non-ABPA) bronchiectasis and severe asthma. The first biological injection was performed at baseline (T0 time). Patients who were already taking LTRA therapy at time T0 were recorded, and no new prescriptions were made. We observed our population over a 6-month period (T1 time). At the baseline we collected the following data: baseline characteristics, clinical history, high resolution computed tomography and bronchiectasis-related parameters and skin prick test. At both times T0 and T1 we collected the following data: asthma control test (ACT), asthma control questionnaire (ACQ), immunoglobulin E (IgE) level, blood count, fractional exhaled nitric oxide 50 (FeNO 50) and flow-volume spirometry. The study was retrospectively registered. RESULTS: Our population had a mean age of 59.08 ± 11.09 and 50% were female. At T1, patients on LTRA therapy had a significantly lower FeNO value (33.03 ± 23.61 vs. 88.92 ± 77.96; p = 0.012). We assessed that the value of ΔFeNO (FeNO 50 T1 - FeNO 50 T0) and the number of unplanned specialist visits allowed a discrimination of 66.7% in the presence of LTRA therapy. We also verified how low FeNO values at time T1 were statistically significant predictors of LTRA therapy (ODD = 9.96 (0.94-0.99); p = 0.032). CONCLUSION: The presence of LTRA in therapy in a population of severe asthmatics with coexisting non-ASBPA bronchiectasis and non-cystic fibrosis, acting simultaneously on the T helper type 2 (TH2) pathway and probably on the neutrophilic component of bronchiectasis, would allow a further amplification of the beneficial effects of biological therapy, leading to a reduction in the number of unplanned visits to specialists.

Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis.

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.

Benralizumab Effectiveness in Severe Eosinophilic Asthma with and without Chronic Rhinosinusitis with Nasal Polyps: A Real-World Multicenter Study.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) affects around 60% of patients with severe eosinophilic asthma (SEA). Benralizumab was recently approved for SEA add-on treatment. OBJECTIVE: To assess the real-world effectiveness of benralizumab in SEA with or without CRSwNP. METHODS: We conducted a multicenter observational study, including patients with SEA treated with benralizumab for 24 weeks in 12 Italian specialized facilities. Asthma exacerbations, Asthma Control Test (ACT), lung function, oral corticosteroid (OCS) dosage, and eosinophil and basophil count in peripheral blood were recorded at baseline and after 4, 12, and 24 weeks. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Mackay scores were assessed at baseline and after 24 weeks in SEA+CRSwNP. RESULTS: A total of 137 patients with late-onset SEA were included; 57.7% (79 of 137) showed the copresence of CRSwNP. Overall, severe asthma exacerbations decreased from 4 (3-6) to 0 (0-2) (P < .0001) after 24 weeks of treatment, and significant improvements were observed as early as 4 weeks in ACT score, OCS dosage, forced expiratory volume in the 1st second (FEV1)%, FEV1 (L), forced vital capacity (FVC)%, FEV1/FVC% (P < .0001), and forced expiratory flow between 25% and 75% of FVC (FEF25-75)% (P = .0022). Eosinophils and basophils in peripheral blood were rapidly depleted. In patients with SEA+CRSwNP, SNOT-22 decreased from 46 (39.5-64.5) to 32 (19-46) (P < .0001). Furthermore, in comparison with SEA, they showed enhanced responses with regard to ACT minimal clinically important difference (P = .0387), FEV1% (P = .017), FEV1 (L) (P = .02), and FEF25-75% (P = .0362). CONCLUSIONS: These real-world data suggest that benralizumab can represent a valid add-on therapeutic option for patients with SEA, especially with comorbid CRSwNP.

The impact of SARS-COV2 pandemic on the management oF IPF patients: Our narrative experience.

BACKGROUND: The SARS-CoV-2 pandemic has changed the health-care systems around the world in a remarkable way. We describe the strategies adopted to cope with the limitations imposed by the pandemic to the access to health care by patients diagnosed with idiopathic Pulmonary Fibrosis (IPF). MATERIAL AND METHODS: We conducted a retrospective observational analysis including IPF patients under antifibrotic drugs (nintedanib and pirfenidone) that accessed to the Outpatient clinic of the University of Palermo, Italy. Patients received a phone number and an email address in case of any urgency and a virtual meeting was settled up monthly. RESULTS: 40 patients (M/F: 30/10) were followed up, 33 under nintedanib treatment, 7 under pirfenidone. Among patients under nintedanib, 1 patient reported high fever (T max 39 °C) and purulent sputum with no sign of infections, 1 had hemoptysis that was spontaneously resolved. 2 patients accessed to the emergency department for the worsening of dyspnea; 5 patients had diarrhea that resolved with symptomatic drugs in few days. 3 patients had an increase of alkaline phosphatase levels, leading to the withdrawal of the antifibrotic drug for 15 days, and subsequent normalization of the plasmatic levels. Among patients under pirfenidone, one subject had an increase of ferritin serum levels with no symptoms. The remaining subjects were in stable clinical conditions. None of the patients reported hospitalization or exacerbations, and did not experience antifibrotic withdrawal. CONCLUSIONS: We were able to demonstrate that by implementing alternative ways to monitor the disease, patients did not incur in increased rates of acute exacerbations or higher frequency of side effects and antifibrotic treatment withdrawal.

The Influence of Smoking Status on Exhaled Breath Profiles in Asthma and COPD Patients.

Breath analysis using eNose technology can be used to discriminate between asthma and COPD patients, but it remains unclear whether results are influenced by smoking status. We aim to study whether eNose can discriminate between ever- vs. never-smokers and smoking <24 vs. >24 h before the exhaled breath, and if smoking can be considered a confounder that influences eNose results. We performed a cross-sectional analysis in adults with asthma or chronic obstructive pulmonary disease (COPD), and healthy controls. Ever-smokers were defined as patients with current or past smoking habits. eNose measurements were performed by using the SpiroNose. The principal component (PC) described the eNose signals, and linear discriminant analysis determined if PCs classified ever-smokers vs. never-smokers and smoking <24 vs. >24 h. The area under the receiver-operator characteristic curve (AUC) assessed the accuracy of the models. We selected 593 ever-smokers (167 smoked <24 h before measurement) and 303 never-smokers and measured the exhaled breath profiles of discriminated ever- and never-smokers (AUC: 0.74; 95% CI: 0.66-0.81), and no cigarette consumption <24h (AUC 0.54, 95% CI: 0.43-0.65). In healthy controls, the eNose did not discriminate between ever or never-smokers (AUC 0.54; 95% CI: 0.49-0.60) and recent cigarette consumption (AUC 0.60; 95% CI: 0.50-0.69). The eNose could distinguish between ever and never-smokers in asthma and COPD patients, but not recent smokers. Recent smoking is not a confounding factor of eNose breath profiles.

Clinical Utility of Midregional Proadrenomedullin in Patients with COVID-19.

OBJECTIVE: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. METHODS: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. RESULTS: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). CONCLUSION: We found that MR-proADM could represent a prognostic biomarker of COVID-19.

Prevalence of Arterial Hypertension and Characteristics of Nocturnal Blood Pressure Profile of Asthma Patients According to Therapy and Severity of the Disease: The BADA Study.

BACKGROUND: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects. METHODS: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM). RESULTS: The overall percentage of asthmatics having also hypertension was 75% (30 patients) vs. 45% (18 patients) of the control group (p: 0.012). Reduced level of FEV1 (but not inhaled steroid therapy) was associated to newly-diagnosed hypertension (p: 0.0002), higher day SBP levels (p: 0.003), higher day DBP levels (p: 0.03), higher 24 h-SBP levels (p: 0.005) and higher 24h-DBP levels (p: 0.03). The regression analysis performed taking into account sex, age, diabetes, fasting glucose, and body mass index confirms the independent role played by asthma: odds ratio (OR): 3.66 (CI: 1.29-11.1). CONCLUSIONS: hypertension is highly prevalent in asthma; the use of ABPM has allowed the detection of a considerable number of unrecognized hypertensives.

Interstitial Lung Disease in Elderly Rheumatoid Arthritis Patients.

The increase in life expectancy together with better care of rheumatoid arthritis (RA) has led to higher proportions of elderly individuals with RA. This has challenged the treatment of the disease in older aged patients, usually characterized by comorbid conditions and polypharmacy. Overall, the lung involvement in RA is present in up to 80% of patients, depending on the assessment tools used, and interstitial abnormalities are among the most common; when present, interstitial lung disease (ILD) worsens the prognosis of RA, and is the second most common cause of mortality. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis of the lung. Therefore, ILD tends to occur more frequently in older patients with RA. The age at onset of RA distinguishes patients as having young-onset RA (YORA, < 60 years) or late-onset RA (LORA, > 60 years); the latter are characterized by more severe features of the disease and higher rates of lung involvement. The most frequent RA-related ILD radiological pattern is usual interstitial pneumonia (UIP); this includes peripheral and basal predominant reticulation and honeycombing with or without associated traction bronchiectasis. Patients with the UIP pattern are usually older and have more rapid decline in lung function and a worse prognosis. Treatment with corticosteroids in elderly patients carries the risk of adverse effects, such as osteoporosis, infections, diabetes, peptic ulcers, and cataract. The use of disease-modifying antirheumatic drugs (DMARDs) is generally well-tolerated by the elderly. The current narrative review aims at elucidating the association between ILD and RA in older individuals.

Early management of COPD: where are we now and where do we go from here? A Delphi consensus project.

PURPOSE: There is a lack of consensus on the most appropriate early diagnostic strategy, criteria for early access to treatment and follow-up approach for patients with COPD. MATERIALS AND METHODS: A Delphi consensus project investigated the early management of COPD. We formulated two questionnaires for completion by pneumologists in Italy. RESULTS: A total of 207 specialists completed questionnaire 1 and 184 of them questionnaire 2, between November 2016 and October 2017. Early diagnosis of COPD was considered uncommon for 93.2% of the expert panel. Regardless of the definition of "early diagnosis" - a diagnosis made before the clinical manifestation of the disease for most responders (60.4%) - experts were confident of the positive effects of early disease management, which they consider is effective in modifying the natural history of the disease. Lack of awareness of the disease was considered the first limiting factor to early COPD management for 78% of respondents. The most effective steps to reduce functional decline were considered to be smoking cessation, followed by long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA), LAMA, LABA, and finally inhaled corticosteroid/LABA (P<0.01 for each paired comparison). Specialists considered it "inappropriate" for general practitioners to perform both the early diagnosis and therapy of COPD without the involvement of a specialist. CONCLUSION: Early management of COPD is uncommon, and although data on the effects of early disease management on long-term outcomes are limited, Italian experts are confident of the clinical efficacy of this approach.

Impact of reslizumab on outcomes of severe asthmatic patients: current perspectives.

Approximately 5%-10% of asthmatics suffer from severe asthma. New biological treatments represent a great opportunity to reduce asthma burden and to improve asthma patients' lives. Reslizumab will soon be available in several European countries. This anti-IL-5 IgG4/κ monoclonal antibody, administered intravenously at a dose of 3 mg/kg over 20-50 minutes every 4 weeks, has been shown to be safe and effective in patients with 400 eosinophils/µL or more in their peripheral blood. The clinical effects in reducing asthma exacerbations and in improving the quality of life and lung function are clear, but further research is needed to determine the best biological compound for a specific cluster of patients. Research data have shown that in patients who were expressing other clinical features of eosinophilic inflammation over asthma (rhinosinusitis and nasal polyposis), the clinical benefit of reslizumab was greater. Furthermore, it has also been observed that in patients with unsatisfactory response to mepolizumab, reslizumab is able to significantly improve the clinical and biological parameters. The aim of personalized medicine is to provide the right drug to the right patient at the right dose at the right moment. The biological treatments that were developed to modify specific pathological pathways not only provide us with the tools for the management of asthma patients but also clarify the biological mechanisms involved in its pathogenesis.

Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance.

The term asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has been proposed for individuals with features of both asthma and COPD. Several attempts have been done to define ACOS on the basis of medical history, symptoms, and functional findings. The main diagnostic criteria include airflow obstruction with a strong although incomplete reversibility to bronchodilation tests, a significant exposure to cigarette or biomass smoke, and a history of atopy or asthma. Additional diagnostic elements include eosinophilic airway and systemic inflammation, a good response to corticosteroid treatment, and a high concentration of exhaled nitric oxide. ACOS should be distinguished from asthma with not fully reversible bronchial obstruction due to airway remodeling, thus the lack of smoking exposure should exclude the diagnosis of ACOS. In patients without a documented history of asthma before 40 years of age, an increase in FEV1 after bronchodilator >400 mL should be required to diagnose ACOS. ACOS has been found to be associated with impaired physical performance, functional ability, and health-related quality of life. The prevalence of ACOS increases with aging, then it is relatively stable in elderly individuals (>65 years). Long-term mortality of subjects with ACOS is similar to COPD, and worse than asthma and healthy controls. Future research is still needed to improve the understanding and management of ACOS.

Withdrawal of inhaled corticosteroids in COPD: A meta-analysis.

BACKGROUND: Conflicting findings exist on the benefit of withdrawal of inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD). We performed a quantitative synthesis in order to assess real impact of ICS discontinuation in COPD patients. METHODS: We carried out a meta-analysis via random-effects model on the available clinical evidence to evaluate the effect of ICS discontinuation in COPD. Randomized clinical trials and observational real-life studies investigating the effects of ICS withdrawal on the risk of COPD exacerbation, lung function (forced expiratory volume in 1 s [FEV1]) and quality of life (St. George's Respiratory Questionnaire [SGRQ]) were identified by searching from published studies and repository databases. RESULTS: ICS withdrawal did not significantly (P > 0.05) increase the overall rate of COPD exacerbation, although a clinically important increased risk of severe exacerbation was detected (Relative Risk >1.2). ICS withdrawal significantly (P < 0.001) impaired both lung function (-30 ml FEV1) and quality of life (+1.24 SGRQ units), although in a non-clinically important manner. The time to the first exacerbation was significantly (P < 0.05) shorter in the patients who discontinued ICS. CONCLUSIONS: The discrepancy between statistical analysis and clinical interpretation of this meta-analytic evaluation demonstrates the strong clinical need in understanding what is the real impact of ICS withdrawal in COPD. ICS discontinuation is a complex procedure that requires a well planned and tailored strategy. Further well designed studies on withdrawal of ICS should be performed by clustering COPD patients with regard to the phenotype characteristics, rate of exacerbations/year, decline of lung function, and quality of life.