Concomitant Asthma Research Articles

Low-dose interleukin-2 in birch pollen allergy: a phase-2 randomized double-blind placebo-controlled trial

Regulatory T cells (Tregs) are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2LD) activates Tregs. To assess IL-2LD efficacy for controlling clinical responses to allergen exposures. RHINIL-2 was a phase-2a, randomised, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included, 66% having concomitant asthma. All had a total nasal symptom score (TNSS) ≥5 following nasal exposure to BP in an environmental-exposure-chamber (EEC). Patients received 1 MUI/day of IL-2 (n=12) or Placebo (n=12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the EEC were evaluated using TNSS, the rhinitis visual analogue scale (VAS) and spirometry. The primary efficacy endpoint was the difference in TNSS area under the curve between inclusion and day 40 (TNSSΔAUC). IL-2LD treatment induced a significant expansion of Tregs. The TNSSΔAUC in the IL-2 and Placebo groups was non significantly different. TNSS and VAS AUCs were significantly reduced from baseline to day 40 in the IL-2LD group only (p=0.04 and p=0.01, respectively). The ratio of forced expiratory volume in 1 second/forced vital capacity (FEV1P) and the forced mid-expiratory flow (FEF25-75%) showed improvement in the IL-2LD vs Placebo groups at day 40 (p=0.04 and 0.04, respectively). However, the short treatment duration used in this study cannot have effects on specific IgE or IgG4 levels given their half-life. There was no severe treatment-related adverse events. IL-2LD is well-tolerated in allergic patients, even with asthma, clearing the path for further therapeutic development. Our work suggests that Treg can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.

Clinical characteristics, use and switch of drugs for obstructive airway diseases among patients with COPD experiencing an exacerbation: a retrospective analysis of Italian administrative healthcare data

BackgroundChronic obstructive pulmonary disease (COPD) represents an important health challenge, despite being preventable and manageable thanks to up-to-date recommendations. In Italy, the pharmaceutical care of COPD patients is still ill-timed and inaccurate. This study aimed to describe the treatment of COPD patients in Italy and possible switches following an exacerbation.MethodsThis observational retrospective analysis of Italian administrative healthcare data from the Fondazione Ricerca e Salute (ReS) database identified patients aged ≥ 45 years with COPD in 2019 and 2020. At least 6 years of look-back period and absence of concomitant asthma were required. COPD patients were categorized by treatment (SI–single/MI–multiple inhalers, TT–triple therapy, DT–dual therapy, other respiratory treatments, untreated) at index date (first dispensation during accrual period). Occurrence of moderate/severe exacerbation during one-year preceding index date and treatments during one-year preceding the exacerbation (possible switch) were evaluated.ResultsFrom ~ 4.7 million beneficiaries of the Italian National Health Service in 2019 and 2020, respectively, 105,828 and 103,729 (43 and 41 × 1,000 inhabitants aged ≥ 45 years) were identified as having COPD. Of 2019/2020 patients: 3.4%/5.2% received SI-TT, 20.7%/17.5% MI-TT, 35.9%/38.1% DT, 33.0%/33.1% other treatments, and 7.0%/6.0% were untreated. Males were prevalent and median age was > 73 years for all groups. Of 2019/2020 cohorts, heart failure and coronary artery disease affected 24/20%, 18/17%, and 11%/16% patients with SI-TT, MI-TT, DT, and other treatments, respectively. A previous moderate/severe exacerbation (2019/2020 patients) occurred to 60.5%/56.6%, 39.9%/37.4%, 30.8%/29.2% and 31.9%/29.7% patients treated with SI-TT, MI-TT, DT, and other treatments, respectively. Of 2019/2020 patients experiencing moderate/severe exacerbation: 6.0%/7.0% receiving DT, 5.1%/7.0% receiving other treatments and 4.5%/10.0% untreated, switched to SI-TT; 23.7%/16.9% receiving DT, 21.4%/17.7% receiving other treatments and 15.4%/12.0% untreated, switched to MI-TT.ConclusionsCOPD patients receiving TT were older and had more comorbidities, especially cardiovascular diseases, than patients receiving DT or other treatments. The limited number of patients switching after exacerbation suggests that many COPD patients may be inappropriately treated. Ensuring early and adequate treatment, combination of in-hospital and outpatient management, and integration of specialist and primary care is pivotal for the appropriate clinical management of COPD patients.

A clinical study on the relationship between chronic rhinosinusitis and bronchial asthma.

To investigate the correlation between chronic rhinosinusitis (CRS) and bronchial asthma, focusing on the CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), as well as their impact on lung function. A total of 141 patients diagnosed with chronic nasal-sinus inflammation were included in this study. Clinical data, including medical histories, nasal endoscopy scores, CT scores, symptom scores, and quality of life assessments, were collected. Among the patients with CRSsNP, 23.8% had concomitant bronchial asthma. The incidence of asthma was significantly associated with the severity of sinus involvement in CRSsNP patients (p = 0.049). Pulmonary function impairment was correlated with the severity of sinus inflammation in CRSsNP patients (p = 0.019). Quality of life was significantly affected in patients with concomitant asthma and CRSsNP or CRSwNP. Chronic rhinosinusitis, both with and without nasal polyps, is closely correlated with bronchial asthma. Pulmonary function impairment is associated with the extent of inflammatory lesions in CRSsNP. Although CRSwNP does not significantly affect pulmonary function, the treatment of sinus diseases can contribute to the control of asthma.

Characteristics of Patients with COPD Initiating Budesonide/Glycopyrronium/Formoterol or Other Triple Therapies in Japan: A Real-World Healthcare Claims Database Study (MITOS-AURA).

In Japan, patients with chronic obstructive pulmonary disease (COPD) can be escalated to treatment with inhaled triple therapy. Two single-inhaler triple therapies combining an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) are approved maintenance therapies for patients with COPD, and multiple-inhaler triple therapies (MITTs) are also available. There is limited evidence regarding real-life treatment patterns and characteristics of patients with COPD initiating triple therapies. This observational, retrospective cohort study identified patients with COPD in Japan from an administrative claims database (May2018-December 2021). Demographics, clinical characteristics, and healthcare resource utilization (HCRU) were assessed in four cohorts initiating a triple therapy: budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) early adopters (initiated ≤ 12months after market approval [September 1, 2019]), contemporary BGF users (initiated > 12months after market approval), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) users, and any MITT users. A total of 636 patients were BGF early adopters, 2558 were contemporary BGF users, 11,187 used FF/UMEC/VI, and 5931 used MITT. The percentage of patients with concomitant asthma in each cohort was 73.0%, BGF early adopter; 74.2%, contemporary BGF; 75.7%, FF/UMEC/VI; and 84.5%, MITT. During the 12-month baseline period, the frequency of patients with ≥ 1moderate/severe exacerbation was 18.2%, BGF early adopter; 14.3%, contemporary BGF; 13.1%, FF/UMEC/VI; and 14.0%, MITT. ICS/LABA treatment during baseline was the most frequent pathway to triple therapy, ranging from 38.2% to 51.7% across cohorts. HCRU was relatively high across cohorts (range of hospital outpatient visits/patient during the 12-month baseline period, 11.0-14.1). Multimorbidity was observed in > 80% of patients in all cohorts; cardiovascular diseases were among the most common. Many patients initiating triple therapy for COPD had concomitant asthma and had previously received ICS/LABA maintenance therapy. Patients prescribed BGF in the initial post-launch period were more likely to have a previous exacerbation history versus other cohorts, indicating more severe disease.

Blood eosinophil count correlates with alveolar damage in emphysema-predominant COPD

BackgroundAlthough blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes.MethodsNinety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens.ResultsThe mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls.ConclusionsSome COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall.

The effect of allergen immunotherapy in patients with central compartment atopic disease post-surgery.

To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post-surgery. A retrospective cohort of surgically treated, HDM-sensitized CRSwNP patients phenotyped as CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use (<4 times/week vs. ≥4 times/week, %) and the rhinologic domain of the 22-item sino-nasal outcome test (SNOT-22). Demographic characteristics, concomitant asthma, smoking status, history of aspirin-exacerbated respiratory disease, conjunctival symptoms, polysensitization, serum eosinophils (cell×109/L), tissue eosinophilia (%>100/HPF), and serum IgE (kU/L) were also recorded. Eighty-six CCAD patients were assessed (41±14yrs, 64% female). AIT was applied in 37% (n=32). Baseline features were similar apart from greater conjunctival symptoms (72 vs. 45%, p=0.02) in the AIT group. At 12 months post-surgery, the AIT group has less MT edema (%≥diffuse 15.6 vs. 52.9, p<0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (%≥4/week, 37.5 vs. 79.6%, p<0.01). The rhinologic symptoms were similar (21.1±17.1 vs. 20.1±21.6, p=0.83). Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de-escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation.

Inhaled Medications for Maintenance Therapy in Pediatric Noncystic Fibrosis Bronchiectasis.

This review focuses on evaluating literature for the use of inhaled mucolytics (hypertonic saline, mannitol, and dornase alfa), inhaled antibiotics (tobramycin, aztreonam, colistin, and amikacin), and inhaled corticosteroids in pediatric noncystic fibrosis bronchiectasis. A literature search via PubMed was conducted using the search terms "non-cystic fibrosis bronchiectasis," "primary ciliary dyskinesia," and "bronchiectasis" in combination with each inhaled agent of interest. Studies were included if they were specific to patients with a clinical diagnosis of noncystic fibrosis bronchiectasis published from 1998 to July 2024. Several inhaled medications can be considered as maintenance therapies for pediatric patients with noncystic fibrosis bronchiectasis. Hypertonic saline could be considered for its potential airway clearance benefits and low risk of causing harm. Inhaled antipseudomonal antibiotics should be considered in patients who are colonized with Pseudomonas aeruginosa. Inhaled corticosteroid therapy should be reserved for patients with concomitant asthma. Dornase alfa has shown worse outcomes in adults with noncystic fibrosis bronchiectasis and should be used with caution. Risks and benefits should be carefully considered when evaluating these therapies for use in noncystic fibrosis bronchiectasis, and patient-specific treatment regimens should be developed. Chronic management of pediatric noncystic fibrosis bronchiectasis remains challenging due to paucity of applicable literature. Risks and benefits of different agents are discussed in this article with recommendations for application to clinical practice based on studies performed in both adult and pediatric patients with noncystic fibrosis bronchiectasis. Several inhaled medications could be considered as maintenance therapies for pediatric patients with noncystic fibrosis bronchiectasis, with more robust evidence to support use of inhaled antipseudomonal antibiotics and hypertonic saline compared with other available agents. Further investigation is needed to identify a clear place in therapy for inhaled therapies in pediatric noncystic fibrosis bronchiectasis.

Biologics for eosinophilic otitis media: a retrospective case study in a multidisciplinary center.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is refractory to conventional treatments and is strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The diagnostic criteria for EOM were established by IINO in 2011. With the recognition of type 2 inflammatory diseases, the gold standard of treatment is the systemic and topical administration of corticosteroids. Recently, several retrospective studies have demonstrated the efficacy of biologic treatments in EOM. We aimed to share our experience regarding the response of EOM after the use of biologics. This is a retrospective observational analysis including patients with refractory EOM treated with different biologics (benralizumab, omalizumab, mepolizumab, dupilumab) for concomitant severe asthma, urticaria and/or severe uncontrolled CRSwNP from 2011 to 2023. Treatment effectiveness in terms of EOM severity was measured using medical Global Evaluation of Treatment Effectiveness (GETE). We illustrated 4 clinical cases of uncontrolled comorbid EOM and demonstrated the complexity of multidisciplinary medical pathway with good response to biologics. We also observed that response to EOM and CRSwNP does not always follow that of asthma. The results of our small sample were consistent with those found in the literature and showed control of EOM with biologics. We need a larger multicentric sample and methodology to confirm these results and to compare the efficacy of different biologics.

Focused allergic rhinitis practice parameter for Canada.

Allergic rhinitis (AR) is a prevalent disease in Canada that affects both children and adults. Several guidelines for the management of AR have been published by professional allergy societies worldwide. However, there are regional differences in the clinical management of AR, and regulatory approval of some AR pharmacotherapies varies among countries. Thus, six research questions specific to the treatment of AR in Canada were identified for this focused practice parameter. Reviews of the literature published since 2016 were conducted to obtain evidence-based support for the responses of the Work Group to each research question. In response to research question 1 "In patients with symptoms indicative of AR, is serum-specific IgE sufficient to identify candidates for immunotherapy or is a skin prick test mandatory?" the Work Group concluded that either sIgE testing or skin prick test are acceptable for diagnosing AR and guiding immunotherapy. In response to research question 2 "When taking into account the preferences of the patient and the prescriber (stakeholder engagement) should second-generation oral antihistamine (OAH) or intranasal corticosteroid (INCS) be first line?" the Work Group concluded that existing guidelines generally agree on the use of INCS as a first-line therapy used for AR, however, patient and provider preferences and considerations can easily shift the first choice to a second-generation OAH. In response to research question 3 "Is a combination intranasal antihistamine (INAH)/INCS formulation superior to INCS plus OAH? Do they become equivalent after prolonged use?" the Work Group concluded that that the combination INAH/INCS is superior to an INCS plus OAH. However, there was insufficient evidence to answer the second question. In response to research question 4 "Do leukotriene receptor antagonists (LTRA) have a greater benefit than OAH in AR for some symptoms to justify a therapeutic trial in those who cannot tolerate INCS?" the Work Group concluded that LTRAs have inferior, or at best equivalent, daytime or overall symptom control compared with OAH, but LTRAs may improve nighttime symptom control and provide benefits in patients with AR and concomitant asthma. In response to research question 5 "Should sublingual immunotherapy (SLIT) tablets be considered first-line immunotherapeutic options over subcutaneous immunotherapy (SCIT) based on the evidence of efficacy?" the Work Group concluded that the choice of SLIT or SCIT cannot be made on efficacy alone, and differences in other factors outweigh any differences in efficacy. In response to research question 6 "Based on efficacy data, should ALL patients seen by an allergist be offered SLIT or SCIT as a treatment option?" the Work Group concluded that the efficacy data suggests that SLIT or SCIT should be used broadly in patients with AR, but other clinical concerns also need to be taken into consideration.

Real world prescription of beta-blockers in patients with asthma.

This study aimed to investigate the prescription of beta-blockers (β-blockers) for patients with asthma. In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, β-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a β-blocker and an asthma medication were co-prescribed in one billing statement or when separate β-blocker and asthma prescriptions had overlapping dates of use. In the 1027 patients with asthma who were prescribed non-selective β-blockers (non-SBs), 3087 non-SB prescriptions were identified, of which 62.3% and 37.3% were for carvedilol and propranolol, respectively. Of the 906 patients with asthma prescribed selective β-blockers (SBs), 2942 SB prescriptions were identified, of which 48.5%, 28.3%, and 20.3% were for bisoprolol, atenolol, and nebivolol, respectively. Overall, 2149 non-SB and 2124 SB prescriptions with overlapping use dates with asthma medications were identified, which were prescribed to 726 and 657 patients, accounting for 70.7% and 72.5% of the patients receiving non-SBs and SBs, respectively. β2-agonists accounted for 39.9% of the concomitant asthma medications with overlapping dates of use with non-SBs. Co-prescribing of bronchodilators occurred at a rate of 38.7% and 45.1% for the 3087 non-SB prescriptions and 2942 SB prescriptions, respectively. Carvedilol and propranolol accounted for half of all β-blockers prescribed to asthma patients. Prescribing β-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between β-blockers and co-prescribed asthma medications.

Real-Life Evidence of Mepolizumab Treatment in Chronic Rhinosinusitis with Nasal Polyps: A Multicentric Study

Background: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. Methods: A retrospective data analysis was jointly conducted at the Otolaryngology–Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow–up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. Results: Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. Conclusions: Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients’ response to biological treatment in CRSwNP.

Exacerbation-like events in the 12 months prior to identification of chronic respiratory conditions in a primary care population

Initial chronic obstructive lung disease (COPD) pharmacotherapy is based on symptom burden and exacerbation history. Inclusion of inhaled cortico-steroids (ICS) is recommended only for those with a history of exacerbations. This brief report highlights that among individuals with previously unrecognized COPD about 1 in 5 have one or more exacerbation-like events and about 1 in 10 have two or more events in the prior 12 months whether or not they self-report concomitant asthma. Closer attention to prior exacerbation-like event history might lead to more guideline concordant care.In addition, there are two other groups that have impaired but non-obstructive spirometry, some with significant respiratory symptom burden who have frequencies of exacerbation-like events similar to those meeting COPD spirometry criteria. To date we have little guidance for treatment of these individuals.

Population Pharmacokinetic Modeling and Exposure-Efficacy and Body Weight-Response Analyses for Tezepelumab in Patients With Severe, Uncontrolled Asthma.

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This analysis assessed the suitability of a fixed-dose regimen of tezepelumab 210 mg every 4 weeks (Q4W) in adults and adolescents with severe, uncontrolled asthma. A population pharmacokinetic model was developed using data from 1368 patients with asthma or healthy participants enrolled in 8 clinical studies (phases 1-3). Tezepelumab exposure-efficacy relationships were analyzed in the phase 3 NAVIGATOR study (NCT03347279), using asthma exacerbation rates over 52 weeks and changes in pre-bronchodilator forced expiratory volume in 1 s at week 52. Tezepelumab pharmacokinetics were well characterized by a 2-compartment linear disposition model with first-order absorption and elimination following subcutaneous and intravenous administration at 2.1-420 and 210-700 mg, respectively. There were no clinically relevant effects on tezepelumab pharmacokinetics from age (≥12 years), sex, race/ethnicity, renal or hepatic function, disease severity (inhaled corticosteroid dose level), concomitant asthma medication use, smoking history, or anti-drug antibodies. Body weight was the most influential covariate on tezepelumab exposure, but no meaningful differences in efficacy or safety were observed across body weight quartiles in patients with asthma who received tezepelumab 210 mg subcutaneously Q4W. There was no apparent relationship between tezepelumab exposure and efficacy at this dose regimen, suggesting that it is on the plateau of the exposure-response curve of tezepelumab. In conclusion, a fixed-dose regimen of tezepelumab 210 mg subcutaneously Q4W is appropriate for eligible adults and adolescents with severe, uncontrolled asthma.

Catching your breath: unraveling the intricate connection between panic disorder and asthma

Respiratory changes are often associated with anxiety disorders, particularly panic disorder (PD). Individuals experiencing PD are subjected to unexpected panic attacks, marked by overwhelming anxiety and fear, leading to a variety of autonomic and respiratory symptoms. PD patients have increased sensitivity to carbon dioxide (CO2). In response to respiratory stimulants like CO2, patients with PD tend to hyperventilate and panic, triggering the activation of an excessively reactive fear network. While their respiratory physiology may appear normal, the presence of subtle breathing abnormalities and other functions related to bodily homeostasis. This fear network, comprising the hippocampus, medial prefrontal cortex, amygdala, and its connections to the brainstem, seems to be hypersensitive in PD’s patients. This review aims to present a comprehensive overview of the current landscape on the link between PD and respiratory disorders. In July 2023 a literature search was undertaken for articles examining the relationship between PD, respiratory disorders, and psychological implications. Multiple databases were searched: PubMed, PubMed Central, PsycINFO, Web of Science, Elsevier Journal, Health &amp; Medical Collection, and Springer. The analysis of six studies focused on the correlation between PD and asthma revealed important links between these two disorders. Anxiety and panic can have significant impacts on the manifestation and aggravation of asthma. Furthermore, the review indicates that psychological therapeutic approaches, in particular cognitive-behavioral therapy, may represent a valid intervention to improve clinical outcomes in patients suffering from both disorders. Future investigations in this field may help highlight new intervention strategies in the psychological area to help individuals with PD decrease concomitant asthma, significantly improving their quality of life.

Real-Life Study of Patient Preference for Dupilumab or Revision Surgery for Recurrent Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high rate of recurrence in patients, despite therapy with local corticosteroids and functional endoscopic sinus surgery. Dupilumab, a recombinant monoclonal human IgG4 antibody directed against the IL-4 receptor α that inhibits both IL-4 and IL-13 signal transduction, is available for symptomatic therapy. Patient preference between repeated surgery and injection therapy with Dupilumab is not known. (2) Methods: Patients who had experienced at least one surgical intervention for nasal polyps and were treated with Dupilumab for at least 3 months completed a retrospective patient questionnaire. (3) Results: In a cohort of 75 previously operated CRSwNP patients, 91.5% preferred therapy with Dupilumab to repeated surgery for nasal polyps. Preference for Dupilumab in the subgroups of patients with concomitant Non-steroidal Anti-inflammatory Drugs Exacerbated Respiratory Disease (N-ERD) (n = 32), patients with concomitant asthma (n = 25), and patients without concomitant disease (n = 18) was 100%, 96%, and 72%, respectively. (4) Conclusions: Patient preference for Dupilumab over repeat surgery is strongest in previously operated CRSwNP patients with concomitant asthma or N-ERD, but remains very high in patients without concomitant disease.

Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC)

BackgroundAsthma is commonly reported in patients with a diagnosis of bronchiectasis. ObjectiveThe aim of this study was to evaluate if patients with asthma and bronchiectasis had a different clinical phenotype and different outcomes compared to patients with bronchiectasis without concomitant asthma. MethodsProspective observational pan-European registry (EMBARC) enrolling patients across 28 countries. Adult patients with CT confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis utilised Cox-proportional hazards regression. Results16963 patients with bronchiectasis were included for analysis. 5267 patients (31.0%) had investigator reported asthma. Patients with bronchiectasis and asthma (BE+A) were younger, more likely to be female and never smokers, and had a higher BMI than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology, but significantly lower severity of disease using the bronchiectasis severity index (BSI). The BE+A group were at increased risk of exacerbation after adjustment for severity of disease and multiple confounders. Inhaled corticosteroid use was associated with reduced mortality in BE+A patients (adjusted hazard ratio 0.78 (0.63-0.95)) and reduced risk of hospitalization, (rate ratio 0.67 (0.67-0.86)) compared to a control population without asthma and not receiving inhaled corticosteroid. ConclusionCombined bronchiectasis and asthma was common and was associated with an increased risk of exacerbations and improved outcomes with inhaled corticosteroid use. Unexpectedly we identified significantly lower mortality in patients with bronchiectasis and asthma.

Upadacitinib improves symptoms of concomitant allergic rhinitis or allergic asthma in patients with severe atopic dermatitis: A 16-week multicentre retrospective study.

Upadacitinib improves symptoms of concomitant allergic rhinitis or allergic asthma in patients with severe atopic dermatitis: A 16-week multicentre retrospective study.

Inhaled Corticosteroids in Subjects with Chronic Obstructive Pulmonary Disease: An Old, Unfinished History.

Chronic obstructive pulmonary disease (COPD) is one of the major causes of disability and death. Maintenance use of inhaled bronchodilator(s) is the cornerstone of COPD pharmacological therapy, but inhaled corticosteroids (ICSs) are also commonly used. This narrative paper reviews the role of ICSs as maintenance treatment in combination with bronchodilators, usually in a single inhaler, in stable COPD subjects. The guidelines strongly recommend the addition of an ICS in COPD subjects with a history of concomitant asthma or as a step-up on the top of dual bronchodilators in the presence of hospitalization for exacerbation or at least two moderate exacerbations per year plus high blood eosinophil counts (≥300/mcl). This indication would only involve some COPD subjects. In contrast, in real life, triple inhaled therapy is largely used in COPD, independently of symptoms and in the presence of exacerbations. We will discuss the results of recent randomized controlled trials that found reduced all-cause mortality with triple inhaled therapy compared with dual inhaled long-acting bronchodilator therapy. ICS use is frequently associated with common local adverse events, such as dysphonia, oral candidiasis, and increased risk of pneumonia. Other side effects, such as systemic toxicity and unfavorable changes in the lung microbiome, are suspected mainly at higher doses of ICS in elderly COPD subjects with comorbidities, even if not fully demonstrated. We conclude that, contrary to real life, the use of ICS should be carefully evaluated in stable COPD patients.

MicroRNA-125b Is a Potential Predictor of Surgical Outcomes in Chronic Rhinosinusitis with Nasal Polyps.

Despite advances in surgical techniques, recurrence rates after endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) remain high and difficult to predict. This study aimed to evaluate the potential role of microRNA 125b (miR-125b) in predicting disease evolution following ESS. We conducted a prospective study including patients undergoing first ESS for CRSwNP in our department between January 2020 and November 2021. We determined miR-125b levels from nasal polyps and pursued a standardized follow-up for at least 18 months for each patient. A total of 86 patients were included in the study. Higher postoperative endoscopy scores were associated with more severe disease at presentation on computed tomography scan, presence of concomitant asthma, and higher values of miR-125b. Even after multivariate repeated measures analysis and adjustments for confounders, miR-125b remained statistically significant. Moreover, miR-125 was the most important factor in predicting disease evolution at 18 months. A clear, robust relation between nasal polyp control evaluated through objective measures and miR-125b values was observed. This finding indicates the potential role of miR-125b in predicting the course of the disease following ESS.

Markers of eosinophilic airway inflammation in patients with asthma and allergic rhinitis.

Background: Measurement of airway inflammation is an important step to determine phenotype of asthma and allergic rhinitis (AR). Objective: To assess the level of nitric oxide in exhaled air (FeNO), nasal fraction of nitric oxide (nasal NO), their relationship with clinical control and blood eosinophils in patients with steroid-naive mild and moderate asthma and AR. Methods: One hundred forty-seven patients (65 men), ages 26-49.5 years (mean age, 32 years) with AR (n = 81) or AR and concomitant asthma (n = 46) and 20 healthy subjects were included in a single-center cohort study. All the patients underwent spirometry with reversibility test. Control of asthma and AR was assessed by using the Asthma Control Questionnaire and the visual analog scale, respectively. Levels of FeNO and nasal NO were measured by chemiluminescent analyzer, peripheral blood eosinophils were counted by automatic analyzer. Results: The FeNO level was significantly elevated in the patients with asthma and concomitant AR compared with the healthy subjects and was associated with control of both asthma and AR. There was no correlation between nasal NO and control of AR. Receiver operating characteristic analysis revealed that the level of eosinophils of 150 cells/μL may be a cutoff for lower airway eosinophilic inflammation. Blood eosinophils count was unable to distinguish eosinophilic and non-eosinophilic upper airway inflammation. Conclusion: We confirm that FeNO but not nasal NO is a marker of eosinophilic airway inflammation in patients with mild-moderate steroid-naive AR and concomitant asthma. A blood eosinophil level of ≥150 cells/µL may be a simple marker of eosinophilic airway inflammation in patients with asthma. However, its low specificity requires repeated measurements and use in combination with other biomarkers.