Nasal Polyposis Quality of Life (NPQ): Development and Validation of the First Specific Quality of Life Questionnaire for Chronic Rhinosinusitis with Nasal Polyps.

To date, no disease-specific tool has been available to assess the impact of chronic rhinosinusitis with nasal polyps (CRSwNP) on health-related quality of life (HRQoL). Therefore, the purpose of this study was to develop and validate a questionnaire specifically designed to this aim: the Nasal Polyposis Quality of Life (NPQ) questionnaire. As indicated in the current guidelines, the development and validation of the NPQ occurred in two separate steps involving different groups of patients. The questionnaire was validated by assessing internal structure, consistency, and validity. Responsiveness and sensitivity to changes were also evaluated. In the development process of NPQ an initial list of 40 items was given to 60 patients with CRSwNP; the 27 most significant items were selected and converted into questions. The validation procedure involved 107 patients (mean age 52.9 ± 12.4). NPQ revealed a five-dimensional structure and high levels of internal consistency (Cronbach's alpha 0.95). Convergent validity (Spearman' coefficient r = 0.75; p < 0.01), discriminant validity (sensitivity to VAS score), and reliability in a sample of patients with a stable health status (Interclass Coefficient 0.882) were satisfactory. Responsiveness to clinical changes was accomplished. The minimal important difference was 7. NPQ is the first questionnaire for the assessment of HRQoL in CRSwNP. Our results demonstrate that the new tool is valid, reliable, and sensitive to individual changes.

Long-term decay of anti-RBD IgG titers after BNT162b2 vaccination is not mirrored by loss of neutralizing bioactivity against SARS-CoV-2.

BACKGROUND AND AIMS: Long-term kinetics of anti-RBD IgG and neutralizing antibodies were analyzed in a cohort of COVID-19 naïve health care workers (HCW) undergoing SARS-CoV-2 vaccination. METHODS: An anti-RBD IgG immunoassay and a surrogate virus neutralization test (sVNT) were performed at different time points up to 6 months after vaccination in 57 HCWs. Values of anti-RBD IgG predicting an high neutralizing bioactivity (>60%) were also calculated. RESULTS: Mean (range) values of anti-RBD IgG were 294.7 (11.6-1554), 2583 (398-8391), 320.4 (42.3-1134) BAU/mL at T1 (21 days after the 1st dose [T0]), T2 (30 days after the 2nd dose) and T3 (+180 days after T0), respectively. Mean (range) percentages of neutralization (NS%) were 24 (0-76), 86 (59-96) and 82 (52-99) at T1, T2 and T3, respectively. Anti-RBD IgG values and NS% were positively correlated at T2 and T3 while anti-RBD IgG value predicting a NS% > 60 markedly differed at T2 and T3 (594 vs. 108 BAU/mL, respectively). CONCLUSION: While a high neutralizing bioactivity was maintained at least 6 months after vaccination in almost all individuals, the mean values of anti-RBD-IgG showed a marked decline at 6 months. The absolute value of anti-RBD IgG is a poor marker of neutralizing bioactivity.

Assessment of humoral and cellular immunity induced by the BNT162b2 SARS-CoV-2 vaccine in healthcare workers, elderly people, and immunosuppressed patients with autoimmune disease.

The development of vaccines to prevent SARS-CoV-2 infection has mainly relied on the induction of neutralizing antibodies (nAbs) to the Spike protein of SARS-CoV-2, but there is growing evidence that T cell immune response can contribute to protection as well. In this study, an anti-receptor binding domain (RBD) antibody assay and an INFγ-release assay (IGRA) were used to detect humoral and cellular responses to the Pfizer-BioNTech BNT162b2 vaccine in three separate cohorts of COVID-19-naïve patients: 108 healthcare workers (HCWs), 15 elderly people, and 5 autoimmune patients treated with immunosuppressive agents. After the second dose of vaccine, the mean values of anti-RBD antibodies (Abs) and INFγ were 123.33 U/mL (range 27.55-464) and 1513 mIU/mL (range 145-2500) in HCWs and 210.7 U/mL (range 3-500) and 1167 mIU/mL (range 83-2500) in elderly people. No correlations between age and immune status were observed. On the contrary, a weak but significant positive correlation was found between INFγ and anti-RBD Abs values (rho = 0.354, p = 0.003). As to the autoimmune cohort, anti-RBD Abs were not detected in the two patients with absent peripheral CD19+B cells, despite high INFγ levels being observed in all 5 patients after vaccination. Even though the clinical relevance of T cell response has not yet been established as a correlate of vaccine-induced protection, IGRA testing has showed optimal sensitivity and specificity to define vaccine responders, even in patients lacking a cognate antibody response to the vaccine.

Community pharmacist's professional adaptation amid Covid-19 emergency: a national survey on Italian pharmacists.

Background Italy has been the first non-Asian country affected by Coronavirus Disease 19 (COVID-19) pandemic. Community pharmacies are essential services authorized to continue their activity during the emergency. To date, a clear image is lacking of the critical issues Italian community pharmacists had to face and of how they responded in their daily work.. Objective To describe procedures and critical logistical-organizational issues encountered by Italian community pharmacists and to collect the main requests reported by patients to pharmacists. Setting A national survey on Italian community pharmacists. Method A cross-sectional survey using a reasoned questionnaire was sent during the pandemic peak to Italian pharmacies, divided in two groups according to the incidence of COVID-19: "Red Zones" and "non-Red Zones". Main outcome measure Exploring the most frequently adopted measures by the pharmacists. Results 169 community Pharmacists answered the questionnaire. The most frequently adopted measures were the use of gloves, surgical masks and protective barriers at the drug counter. Most implemented services for customers were: booking of prescriptions, delivery of medications and implementation of phone consultations. Overall, the questionnaire highlighted an increase in the number of health-related consultations and requests by customers. In Red Zones, there was a higher use of FFP2 and FFP3 masks by pharmacists, where customers were mainly interested in gaining information about specific classes of medications. Conclusion Community pharmacists adapted to lockdown measures by implementing a number of measures. There was an overall increase in pharmacists' personal protective equipment in Red Zones possibly linked to increased risk perception.

Allergen immunotherapy and biologics in respiratory allergy: friends or foes?

PURPOSE OF REVIEW: Allergen-specific immunotherapy has established as an indispensable disease-modifying treatment in allergy practice but its safety and efficacy might be furtherly improved by combining it with other drugs or therapeutic intervention that co-modulate immune type 2 immune networks. RECENT FINDINGS: In the past two decades, clinical research focused on AIT and omalizumab co-treatment to improve both safety and long-term efficacy of allergic disease treatment. Recently, combination of AIT with other biologicals targeting different mediators of type 2 inflammation has been set up with interesting preliminary results. Moreover, AIT current contraindication might be overcome by contemporarily controlling underlying type 2 inflammation in severe atopic patients. SUMMARY: AIT--biological combination treatment can realize a complex multitargeted treatment strategy allowing for consistently improving disease control and sparing steroid administration.

Gastroesophageal reflux and asthma: when, how, and why.

PURPOSE OF REVIEW: Gastro-esophageal reflux is a possible cause of uncontrolled symptoms of asthma and should be actively investigated and treated before severe asthma is diagnosed and biological therapy started. RECENT FINDINGS: Recent investigations on esophageal function and tissue biomarkers in patients with asthma and associated GERD have established a relevant role for esophageal motility and neuronal sensory abnormalities in linking the two diseases. Characterization of the underpinning inflammatory substrate has showed mixed results as both neutrophilic and eosinophilic type 2 inflammatory changes have been described. SUMMARY: New findings regarding inflammatory mechanisms in GERD-associated asthma as well as new diagnostic tools to investigate functional esophageal abnormalities and characterize asthma endotype have identified potential treatable traits that may improve the clinical management and outcome of asthmatic patients with GERD.

Clinical features associated with a doctor-diagnosis of bronchiectasis in the Severe Asthma Network in Italy (SANI) registry.

BACKGROUND: Several severe asthma comorbidities have been identified: an emerging one is bronchiectasis. We evaluated the frequency of bronchiectasis on severe asthma in a real-life setting, through the 'Severe Asthma Network Italy' (SANI) registry. METHODS: SANI registry encompasses demographic, clinical, functional and inflammatory data of Italian severe asthmatics. Data obtained by the enrolled patients were analyzed, focusing the attention on those patients with concomitant clinically relevant bronchiectasis. RESULTS: About 15.5% patients have bronchiectasis. Bronchiectasis diagnosis was associated with a higher prevalence of chronic rhinosinusitis with nasal polyps (54.6% vs. 38%, p = 0.001) and higher serum IgE levels (673.4 vs. 412.1 kUI/L, p = 0.013). Patients with bronchiectasis had worse asthma control (ACT: 16.7 vs 18.2, p = 0.013), worse quality of life (AQLQ: 4.08 vs. 4.60, p = 0.02) and lower lung function (FEV1% predicted 67.3 vs. 75.0, p = 0.002). A higher rate of severe asthma exacerbations in the previous 12 months (85.2% vs. 61.5%, p < 0.001) was found in patients with bronchiectasis. CONCLUSION: severe asthma associated with bronchiectasis represents a particularly severe asthma variant, possibly driven by an eosinophilic endotype. We, therefore, suggest that bronchiectasis should necessarily be assessed in severe asthmatic patients.

Extended nitric oxide analysis in patients with chronic rhinosinusitis with nasal polyps, with or without associated asthma.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease highly impacting patient's quality of life, and associated with lower airway inflammation often evolving into asthma. Exhaled nitric oxide (FENO) is a non-invasive tool to assess Type 2 airway inflammation and its extended analysis allows to differentiate between alveolar concentration (CalvNO) and bronchial output (JawNO). It is also possible to assess the sino-nasal production of nitric oxide (nNO). We studied extended nitric oxide production in patients with CRSwNP with or without associated asthma. Consecutive adult patients with CRSwNP, with or without asthma, and 15 healthy controls were enrolled. Exclusion criteria were: smoking, uncontrolled asthma, recent upper or lower airway infections and oral corticosteroid therapy in the 4 weeks preceding clinical evaluation. Patients' demographic and clinical data were collected; patients underwent pulmonary function tests and extended nitric oxide analysis including nasal nNO assessment. A total of 125 subjects were enrolled (15 healthy controls; 69 with CRSwNP and asthma, and 41 with CRSwNP only). FENO, JawNO and CalvNO values were higher, while nNO was lower, in all patients with CRSwNP compared to healthy controls; no difference was found in CalvNO between patients with concomitant asthma and non-asthmatic subjects; in asthmatic patients, FENO and JawNO were significantly higher, while nNO values was lower, compared to patients with CRSwNP only. These results suggest that CRSwNP could be the first manifestation of a more complex systemic inflammatory pathology driven by Type 2 inflammation. An 'inflammatory gradient' hypothesis could describe a pattern of inflammation in CRSwNP patients that starts distally in the alveoli. Finally, our study indirectly reinforces the concept that novel biological drugs could become valid therapeutic options for nasal polyposis.

Effect of an educational intervention delivered by pharmacists on adherence to treatment, disease control and lung function in patients with asthma.

BACKGROUND: Lack of therapeutic adherence is a relevant problem in clinical practice and it can be assessed via validated tools such as the Test of Adherence to Inhalers (TAI). Education on the correct use of inhaler devices has been associated with improvement in adherence. Many studies highlighted the pivotal role of pharmacists in promoting therapeutic adherence in the management of respiratory diseases. OBJECTIVE: To evaluate the effectiveness on adherence and clinical parameters of an educational intervention administered by clinical pharmacists (CPs) to patients with asthma on long-term inhalation therapy. METHODS: A prospective comparative study involving 34 community pharmacies in Italy (23 intervention, 11 control). Enrolled subjects were evaluated for adherence to inhalation therapy by TAI, asthma control by "Asthma Control Test" (ACT), and lung function at baseline and after 2 months. The educational intervention at baseline was based on TAI results and administered by specifically trained pharmacists. RESULTS: A total of 242 consecutive subjects (167 intervention, 75 control) were enrolled. There was a significant improvement in TAI score, ACT and lung function parameters (p-value<0.001) in the intervention group between baseline and the follow-up visit. Patients with baseline ACT≥20 maintained disease control more frequently in the intervention group compared to the control arm (95% vs 79.5%, p = 0.004). Conclusions through administration of TAI-driven educational interventions addressing both technical and psychological issues, trained CPs can help improve adherence to treatment and asthma control.

Allergy clinics in times of the SARS-CoV-2 pandemic: an integrated model.

BACKGROUND: Almost the entire World is experiencing the Coronavirus-Disease-2019 (COVID-19) pandemic, responsible, at the end of May 2020, of more than five million people infected worldwide and about 350,000 deaths. In this context, a deep reorganization of allergy clinics, in order to ensure proper diagnosis and care despite of social distancing measures expose, is needed. MAIN TEXT: The reorganization of allergy clinics should include programmed checks for severe and poorly controlled patients, application of digital medicine service for mild-to-moderate disease in well-controlled ones, postponement of non urgent diagnostic work-ups and domiciliation of therapies, whenever possible. As far as therapies, allergen immunotherapy (AIT) should not be stopped and sublingual immunotherapy (SLIT) fits perfectly for this purpose, since a drug home-delivery service can be activated for the entire pandemic duration. Moreover, biologic agents for severe asthma, chronic spontaneous urticaria and atopic dermatitis should be particularly encouraged to achieve best control possible of severe disease in times of COVID-19 and, whenever possible, home-delivery and self-administration should be the preferred choice. CONCLUSION: During COVID-19 pandemic, allergists have the responsibility of balancing individual patients' needs with public health issues, and innovative tools, such as telemedicine and digital medicine services, can be helpful to reduce the risk of viral spreading while delivering up-to-date personalized care.

Siltuximab in relapsed/refractory multicentric Castleman disease: Experience of the Italian NPP program.

Because of the rarity of the disease, randomized clinical trials for multicentric Castleman disease (MCD) remain a challenge and, as a consequence, there is no established standard of care. Siltuximab is a chimeric immunoglobulin G1κ monoclonal antibody against human IL-6 which was recently approved by FDA. Eligible patients in Italy were granted early access through a Named Patient Program (NPP). The aim of this observational multicenter retrospective study was to analyze outcomes and toxicity data of relapsed or refractory MCD patients treated with siltuximab in a real life context. All the 9 patients who received siltuximab in Italy under the NPP were enrolled. Median duration of treatment was 285 days (range, 104-1113 days). The global overall response rate was 33.3%. At the time of this analysis, none of the 3 responder patients had subsequently disease relapse: response duration was 20, 23, and 37 months, respectively. Grade 1 to 2 fatigue and pruritus were observed in 2 (22.2%) patients, and weight gain was reported in only 1 patient (grade 1); local edema was reported in 2 patients with a grade 2 presentation. The most common side effect was upper respiratory tract infection reported in 3 (33.3%) patients but in these cases was grades 1 to 2. No patient developed an infusion-related reaction. Our NPP data support siltuximab as single agent in the real-life experience of the treatment of relapse/refractory MCD patients in effectiveness, safety profile, and sustained disease control.