Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.

Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab.

BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

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.

Is mild asthma in real life always in the Green Zone?

Asthma is a chronic inflammatory disease of the airways that is characterized by variable narrowing of the airways and symptoms of intermittent dyspnea, wheezing, and nighttime or early-morning coughing. Asthma is a major health problem throughout the world, affecting an estimated 315 million persons of all ages. Asthma is clinically heterogeneous, and its pathophysiology is complex. For convenience, asthma action plans are often broken down into three zones, usually based on peak flow meter recordings: green, yellow, and red according to the level of lung function impairment. Recent evidence shows that every asthmatic is potentially at risk for severe exacerbation independently of his/her zone, including the green zone. Furthermore, in real life scenario asthmatic patients can have poor perception of their symptoms or/and overestimate their level of asthma control, and this can obviously confound the clinical picture and favor sudden worsening of symptoms. To understand how to treat these patients, as well as how to assess their future risk, can make a difference in terms of clinical outcomes and prognosis. Following the suggestions and concerns recently published, who recently focused on the clinical management of mild asthma, we aimed at exploring strengthens and gaps in the daily management of the mildest forms of the disease, with a focus on alternative diagnostic and therapeutic strategies in approaching the "green" patient in clinical practice.

Adherence to inhaled corticosteroids and long-acting ß2-agonists in asthma: A MASK-air study.

INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting ß2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.

Identification by cluster analysis of patients with asthma and nasal symptoms using the MASK-air® mHealth app.

BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.

Comorbid allergic rhinitis and asthma: important clinical considerations.

INTRODUCTION: The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequently coexist in the same patient and share numerous pathogenetic and pathophysiological mechanisms. AREAS COVERED: We reviewed major pathophysiological, epidemiological, and clinical links between allergic rhinitis and asthma. We also provided a comprehensive discussion of allergic rhinitis treatment according to current guidelines, with a particular focus on the relevance of allergic rhinitis therapies in patients with comorbid asthma. EXPERT OPINION: We believe that there are several unmet needs for our patients, however, there are promising advances forecasted for the future. Although allergic rhinitis is a recognized risk factor for asthma, a proper asthma detection and prevention plan in allergic rhinitis patients is not available. Allergen immunotherapy (AIT) represents a promising preventive strategy and may deserve an earlier positioning in allergic rhinitis management. A multidisciplinary approach should characterize the journey of patients with respiratory allergies, with an adequate referral to specialized Allergy/Asthma centers. Molecular Allergy Diagnosis may provide support for optimal AIT use. Finally, a possible evolution of biological treatment can be envisaged, mainly if biosimilars decrease such therapies' costs.

Monophosphoryl lipid A (MPL) promotes allergen-induced immune deviation in favour of Th1 responses.

BACKGROUND: Monophosphoryl lipid A (MPL) is a nontoxic derivative of the lipopolysaccharide (LPS) of Salmonella minnesota R595. MPL has been used as an adjuvant in grass and tree pollen vaccines for the treatment of seasonal allergic rhinitis. Little is known about the influence of MPL on cellular responses to allergens in man. We therefore studied the effects of MPL in vitro on peripheral blood mononuclear cells (PBMC) obtained from patients with grass pollen hay fever. METHODS: The PBMCs from 13 subjects were cultured with grass pollen Phleum pratense extract (0, 2 and 20 microg/ml) and MPL (0 and 10 microg/ml; defined as an optimal concentration in preliminary studies) and after 6 days proliferative responses were measured by thymidine incorporation and cytokine production by enzyme-linked immunosorbent assay (ELISA). RESULTS: Proliferative responses were unaffected by the presence of MPL whereas MPL induced a significant increase in allergen-induced interferon (IFN)-gamma production [allergen alone, 645 +/- 466 pg/ml (mean +/- SE) vs allergen + MPL, 3232 +/- 818 pg/ml; P < 0.001]. In addition, there was a significant decrease in interleukin (IL)-5 production (4307 +/- 1030 pg/ml vs 2997 +/- 826 pg/ml; P < 0.01). Although MPL alone could induce modest increases in IL-10 production, MPL did not influence the production of this cytokine in allergen-stimulated cultures. Addition of neutralizing antibody against IL-12 resulted in 95% inhibition of MPL-induced IFN-gamma production. Depletion of monocytes from the culture system abrogated the effects of MPL on elevated cytokine production. CONCLUSIONS: In summary, use of MPL with grass pollen extract results in immune deviation of allergen-induced peripheral Th2-cell responses in favour of 'protective' Th1 responses in an IL-12 and monocyte-dependent fashion.

Variations in serum levels of interleukin (IL)-1beta, IL-2, IL-6, and tumor necrosis factor-alpha during specific immunotherapy.

BACKGROUND: Cytokine production by T helper cells is essential for the induction and maintenance of allergic inflammation in the bronchial mucosa. According to recent views, specific immunotherapy (SIT) favors the differentiation of T lymphocytes into cells of the Th1 rather than those of the Th2 subset. OBJECTIVE: To determine whether or not SIT induces a decrease in the inflammatory reaction by studying eventual variations in the serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha in allergic subjects during SIT. METHODS: Serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha were determined before and after 3, 6, and 9 months of SIT by an immunoradiometric assay (IRMA) in 11 adults with perennial allergic asthma and/or rhinitis caused by house dust mites and in 6 nonatopic healthy volunteers. RESULTS: Median serum IL-1beta and TNF-alpha levels of the patients were significantly higher at baseline than those of the controls and decreased during SIT to values similar to or lower (P < .01) after 6 months of SIT for TNF-alpha than those of the controls. Median serum IL-2, significantly lower at baseline than in the controls, increased during SIT to a level similar to that of the controls. Although the median values of IL-1beta and TNF-alpha in the patients tended to decrease and those of IL-2 to increase during SIT, the differences were not significant; the correlation coefficients (r) of the serum levels of IL-1beta IL-6, and TNF-alpha versus duration of SIT were negative, while that of IL-2 was positive. CONCLUSIONS: Decreases in median serum IL-1beta and TNF-alpha levels during SIT, together with the increases in serum IL-2 and IL-6, compared with those of the controls furnish evidence supporting a reduction in the inflammatory response in the course of SIT.

VEP pattern reversal in the assessment of optic nerve function in diabetics.

The visual evoked potentials (VEP pattern) were studied in a group of 18 type I diabetic subjects. Age of patients, duration of disease, glicosilated hemoglobin, blood sugar were correlated with the modifications in latency and amplitude of visual evoked responses.