Immunoglobulin free light chains in severe asthma patient: Could they be a new biomarker?

BACKGROUND: Increasing evidence is available about the presence of increased serum concentration of immunoglobulin (Ig) free light chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease. METHODS: We analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein) was detectable. RESULTS: FLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-λ levels, the FLC-k/FLC-λ ratio displayed remarkable differences between the two groups. A positive correlation between FLC-κ and FLC-λ levels was found. FLC- λ level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-κ /FLC- λ ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization. CONCLUSIONS: Our findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-κ and FLC-k/FLC-λ ratio could be a qualitative indicator for asthma, while FLC-λ levels could be a quantitative indicator for clinical severity parameters.

Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness.

OBJECTIVE: The present study evaluated the safety and efficacy of dupilumab in severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). PATIENTS AND METHODS: A retrospective analysis was conducted on a cohort of adult patients affected by severe CRSwNP treated with dupilumab. Maxillofacial computed tomography, evaluation of blood eosinophils and serum IgE levels, measurement of nasal polyp score (NPS), smell identification test (SSIT-16), sinonasal outcome test-22 (SNOT-22) and asthma control test (ACT) were performed. Follow-up was conducted at 2 weeks, and at 1, 3, and 6 months. Adverse events and the efficacy of treatment were monitored. RESULTS: 23 patients were enrolled. After 15 days, scores of the SNOT-22, NPS and SSIT-16 significantly improved. These outcomes were also maintained after 1, 3, and 6 months (p < 0.001). At this latter follow-up time, SNOT-22 showed a change of -33.10 (p < 0.001), NPS -3.36 (p < 0.001) and SSIT-16 +5.60 (p < 0.001). In all, 26.1% of patients experienced early minor complications. CONCLUSIONS: In the present study, dupilumab was effective in the treatment of severe uncontrolled CRSwNP, demonstrating a quick significant improvement in both questionnaires and endoscopic evaluation. Only minor complications were observed.

The role of mobile apps in allergic respiratory diseases: an Italian multicentre survey report.

Summary: We performed a multicentre survey about the role of mobile apps in allergic respiratory diseases. The main objective was to investigate the current use and usefulness of mobile phone apps in the management of allergic respiratory disease. An original questionnaire including 12 multiple-choice questions was administered to 360 participants (153 male and 207 female subjects). Of notice, 290 subjects owned a smartphone, 120 a personal computer and 68 a tablet (multiple answers were possible). 123 subjects reported to be regular mobile-apps users, 209 were occasional users and 76 has never downloaded an app. Indeed, 259 subjects have never dealt with a medical or healthcare app, with only 8 subjects answering to often take advantage of such supportive tools. Data were even more discouraging when asking whether subjects had ever downloaded an app directly related to their own medical condition (allergy, asthma and rhinitis). 87.2% provided a negative answer. Among the few individuals who reported a previous experience with allergy/asthma apps only 2 subjects reported to regularly use the apps they had downloaded, even after months. The majority of subjects believed the apps would provide a relevant support, but only 25/360 participants found that the apps are "truly helpful", while 44 considered them of "help but not essential". Our data seem to show that the apps in the medical field, especially for allergic respiratory diseases, are welcome by patients, but their continued use and utility wane with the passage of time from the date of the download. In the future it will therefore be important to focus on the quality of the apps themselves and on the careful selection of the most suitable patients to use them. Finally, it will be important to make use of the fundamental contribution of healthcare professionals for the development of the apps.

Association Between the Serum Uric Acid Levels and Lacunar Infarcts in the Elderly.

Increasing evidence suggests that uric acid (UA) is a relevant risk factor for arteriolosclerosis and recent studies have demonstrated the positive relationship between UA concentrations and the severity of leukoaraiosis. However, the association between lacunar infarcts (LI) and UA levels has seldom been reported in the literature. The aim of our study was to assess whether serum UA levels may be related to the presence of LI. We recruited 242 patients (113 males and 129 females, aged 82.83 ± 6.49 years) from our Geriatric Department for whom CAT scans (CT) were available. Clinical and laboratory data was collected. Patients CT images were examined to identify the presence, the size, the number, and the location of LI. LI without neurological symptoms were considered silent LI. Serum UA levels were found to be positively associated with the presence (p = 0.0001), the number (p = 0.001), the size (p = 0.001), and the location of LI in the basal ganglia (p = 0.0038), the deep white matter (DWM) (p < 0.0001), and the pons (p = 0.0156). A significant association was also found between UA and silent LI (p = 0.0002). The prevalence of LI increased starting from UA levels of 5.7 mg/dl. Stepwise multiple regression analysis confirmed that UA was independently related with the presence, the number, the size, LI in the basal ganglia, the DWM, the pons, and with silent LI. Our study suggests a positive association between UA levels and LI, which is independent of traditional cardiovascular risk factors. This data suggests that UA plays an influential role on the physiopathology of LI and could represent a potential target to prevent cerebral microinfarcts.

Nasal cytology: Methodology with application to clinical practice and research.

Nasal cytology is an easy, cheap, non-invasive and point-of-care method to assess nasal inflammation and disease-specific cellular features. By means of nasal cytology, it is possible to distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non-allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time-course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non-allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic-mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non-invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology.

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study.

BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. METHODS: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. RESULTS: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study.

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.

Evaluation of asthma control in the pharmacy: an Italian cross-sectional study.

SUMMARY: Background. In Western countries a large proportion of asthmatic patients remain uncontrolled, despite the availability of effective drugs. An involvement of pharmacies / pharmacists in asthma management has been suggested in guidelines, since this could provide a relevant support. Objective. The present cross-sectional study aimed at assessing the level of asthma control, by using ACT questionnaire, in the community pharmacies in the County of Verona, North East of Italy. Methods. A call for participation was sent by Verona Pharmacists' Association to all the pharmacies located in the Verona municipality. Patients with a medical prescription and an asthma exemption code were recruited in pharmacies. They were asked to fill the ACT questionnaire and to answer some additional questions on asthma treatment, smoke habits and comorbidities. Results. Thirty-seven community pharmacies recruited 239 patients. According to the ACT score, more than 50% of patients had a controlled asthma but 20% of them were totally uncontrolled and 12% were using oral steroid. Only 2.9% of patients had received an asthma action plan. Asthma was intermittent in 17.6% of patients, mild persistent in 13.8%, moderate persistent in 63.1% and severe in 5.4%. Discordance was observed between the self-perceived asthma control and objective parameters, when available. Of note, in the severe asthma group, most patients had an ACT > 20. Conclusion. This is the first Italian pharmacy-based study on asthma control. A better asthma control was recorded in this study in comparison with other trials, but about 50% of patients were insufficiently controlled. The community pharmacies can play a relevant role in the preliminary assessment of asthma control by using easy and not time consuming tools, such as ACT.

Validation of the MASK-rhinitis visual analogue scale on smartphone screens to assess allergic rhinitis control.

BACKGROUND: Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients. OBJECTIVE: The aim of this study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) app (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control. METHODS: Each user filled 4 different VAS measuring overall, nasal, ocular, and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity, and acceptability of the MASK-Rhinitis VAS. RESULTS: Between 1 August 2015 and 31 July 2016, the app was used 14 612 times in 15 countries. A total of 1225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test > 0.84, test-retest > 0.7), reliability (>0.9), and acceptability. In addition, the tool had a good sensitivity when users (n = 521) answered the VAS twice in less than 3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.

Allergic and nonallergic rhinitis and skin sensitization to metals: is there a link?

SUMMARY: Background. Chromium, Cobalt and Nickel are responsible for contact dermatitis, that is largely prevalent in the general population. They can act also as irritants in the upper and lower respiratory airways. Also rhinitis (allergic and nonallergic) is a high prevalence disorder. Both diseases could share some common inflammatory mechanisms, but the clinical association between skin sensitization to metals and rhinitis was never studied. Objective. We assessed the presence of skin sensitization to metals in subjects with rhinitis. Methods. Patients suffering from rhinitis underwent a standard diagnostic procedure, including skin testing, nasal endoscopy and nasal cytology. Control healthy subjects were also included. None of the patients had skin diseases. All subjects underwent patch test with Chromium, Cobalt and Nickel. Results. None of the 26 controls had positive skin prick test or nasal cytology. The 82 rhinitis patients were subdivided into allergic (group A = 27), nonallergic (group B = 31) and overlapping (group C = 24). The prevalence of positive patch test to metals was 26% in group A, 45% in group B, 42% in group C and 31% in controls. The percentage of patch-positive subjects was significantly different between Group A and B (p = 0.0045; OR: 0.43), Group A and C (p = 0.0186; OR: 0.49), and Group B and controls (p = 0.0360; OR: 1.85). There was a significant difference between groups A + controls and B + C. Conclusion. Even in the absence of skin diseases, the prevalence of sensitization to metals (patch test) is greater in nonallergic and overlapping rhinitis, as compared to allergic rhinitis and controls.

Why a registry of Chronic Urticaria (CUR) is needed.

Chronic urticaria (CU) has a major effect on patients' quality of life. While there have been progressive advances regarding its pathogenesis and treatment, much remains to be done. Registries of other chronic non-communicable diseases have shown many benefits, such as additional basic knowledge and management approaches to diabetes mellitus. Standards of care as well as diagnostic approaches can be elaborated and compared from different sites, using validated instruments. Registries in allergic diseases are also becoming well recognized, and the first registry on CU, accessible from SLaai's webpage, includes parameters for identification, evaluation and management. In our vision, informatics strategies have the potential to improve care for chronic illnesses such as CU. The registry represents a valid instrument from which to obtain a sufficient sample size for epidemiological studies and/or clinical research planning, including feasibility and potential enrollment. It can also provide invaluable data for adapting guidelines to local populations, as well as diagnostic approaches and cost-effective interventions in the context of organizational efforts to improve patient care.

Work productivity in rhinitis using cell phones: The MASK pilot study.

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.