Histamine is the primary mediator involved the pathophysiology of allergic rhinitis and chronic urticaria, and this explains the prominent role that histamine H₁‐receptor antagonists have in the treatment of these disorders. However, histamine is clearly not the only mediator involved in the inflammatory cascade. There is an emerging view that drugs which can inhibit a broader range of inflammatory processes may prove to be more effective in providing symptomatic relief in both allergic rhinitis and chronic urticaria. This is an important consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative which provides a scientific basis for defining what are the desirable properties of an ‘ideal’ antihistamine. In this review of rupatadine, a newer dual inhibitor of histamine H₁‐ and PAF‐receptors, we evaluate the evidence for a mechanism of action which includes anti‐inflammatory effects in addition to a powerful inhibition of H₁‐ and PAF‐receptors. We assess this in relation to the clinical efficacy (particularly the speed of onset of action) and safety of rupatadine, and importantly its longer term utility in everyday life. In clinical trials, rupatadine has been shown to be an effective and well‐tolerated treatment for allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of action, producing rapid symptomatic relief, and it also has an extended duration of clinical activity which allows once‐daily administration. In comparative clinical trials rupatadine was shown to be at least as effective as drugs such as loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms in adult/adolescent patients with seasonal, perennial or persistent allergic rhinitis. Importantly, rupatadine demonstrated no adverse cardiovascular effects in preclinical or extensive clinical testing, nor negative significant effects on cognition or psychomotor performance (including a practical driving study). It improved the overall well‐being of patients with allergic rhinitis or CIU based on findings from quality of life questionnaires and patient global rating scores in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of histamine H₁‐ and PAF‐receptors, which has been shown to be an effective and generally well‐tolerated treatment for allergic rhinitis and chronic urticaria. It possesses a broader profile of anti‐inflammatory properties inhibiting both inflammatory cells and a range of mediators involved in the early‐ and late‐phase inflammatory response, but the clinical relevance of these effects remain to be clarified.

Asthma and obesity are two epidemics affecting the developed world. The relationship between obesity and both asthma and severe asthma appears to be weight-dependent, causal, partly genetic, and probably bidirectional. There are two distinct phenotypes: 1. Allergic asthma in children with obesity, which worsens a pre-existing asthma, and 2. An often non allergic, late-onset asthma developing as a consequence of obesity. In obesity, infiltration of adipose tissue by macrophages M1, together with an increased expression of multiple mediators that amplify and propagate inflammation, is considered as the culprit of obesity-related inflammation. Adipose tissue is an important source of adipokines, such as pro-inflammatory leptin, produced in excess in obesity, and adiponectin with anti-inflammatory effects with reduced synthesis. The inflammatory process also involves the synthesis of pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and TGFβ, which also contribute to asthma pathogenesis. In contrast, asthma pro-inflammatory cytokines such as IL-4, IL-5, IL-13, and IL-33 contribute to maintain the lean state. The resulting regulatory effects of the immunomodulatory pathways underlying both diseases have been hypothesized to be one of the mechanisms by which obesity increases asthma risk and severity. Reduction of weight by diet, exercise, or bariatric surgery reduces inflammatory activity and improves asthma and lung function.

Background: About one‐tenth of patients with difficult‐to‐treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (NSAID‐ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)‐4/IL‐13 receptor component, is an approved add‐on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID‐ERD.Methods: Data were pooled from the phase 3 SINUS‐24 and SINUS‐52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment–subgroup interactions were assessed for patients with and without NSAID‐ERD.Results: Of 724 patients, 204 (28.2%) had a diagnosis of NSAID‐ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund–Mackay computed tomography, 22‐item Sinonasal Outcome Test (SNOT‐22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six‐item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p < .0001) in patients with NSAID‐ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID‐ERD for NC (p = .0044), SNOT‐22 (p = .0313), TSS (p = .0425), and PNIF (p = .0123).Conclusions: In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient‐reported symptoms to a greater extent in the presence of comorbid NSAID‐ERD than without. Dupilumab was well tolerated in patients with/without NSAID‐ERD.

Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with a strong antagonist activity towards both histamine H(1) receptors and platelet-activating factor receptors. The use of rupatadine is indicated in adult and adolescent patients (> 12 years of age) suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. In the treatment of these diseases, rupatadine is at least as effective as ebastine, cetirizine, loratadine and desloratadine. A very good safety profile of rupatadine has been evidenced in various studies, including a long-term (1-year) safety study. Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine and lorazepam, but should not be administered concomitantly with known CYP3A4 inhibitors.

Background: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors α (GRα) and β (GRβ). A study was undertaken to assess GRα and GRβ expression in steroid insensitive interstitial lung disease (idiopathic pulmonary fibrosis (IPF)) and steroid sensitive interstitial lung diseases (sarcoidosis and cryptogenic organising pneumonia (COP)). Methods: Lung tissue was obtained from control subjects and from patients with IPF, sarcoidosis, and COP. Pulmonary function tests were carried out at the time of lung biopsy and every 3 months. GRα and GRβ expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25–75th percentile. Results: GRα mRNA expression (10⁵ cDNA copies/µg total RNA) was higher in patients with steroid sensitive interstitial lung diseases (10.0; 7.8–14.9; n = 11) than in patients with IPF (4.4; 3.2–6.6; n = 19; p<0.001). GRβ expression was at least 1000 times lower than that of GRα and did not differ between the three groups. A negative correlation was found between GRα mRNA levels and the fibrotic pathology score of the tissue (r = −0.484, p<0.01) and a positive correlation was found between GRα mRNA levels and improvement in forced vital capacity (r = 0.633; p<0.01) after treatment of patients with glucocorticoids. Immunoreactivity for GR protein was also higher in patients with sarcoidosis and COP than in those with IPF. Conclusion: The variable response of some interstitial lung diseases to steroid treatment may be the result of differences in the expression of GRα.