Current treatment strategies for seasonal allergic rhinitis: where are we heading?

INTRODUCTION: Allergic rhinitis (AR) is very commonly caused by pollens. The symptoms of AR consist of sneezing, nasal congestion, rhinorrhea, nasal itching and airflow obstruction. The diagnosis has long been based on clinical history, skin prick tests and in vitro measurement of specific IgE, but the innovative approach of precision medicine has made diagnostic tools of much greater accuracy available. AREAS COVERED: This review covers the advances in the treatment of seasonal AR concerning the drugs to be used according to the grade of disease and the characteristics of the patients, and the role of allergen immunotherapy (AIT), which is the only treatment capable of acting, in addition to the symptoms, on the cause of AR and therefore to modify its natural history. EXPERT OPINION: Drug treatment of AR include a large number of agents, the choice of which depends on the severity of the disease. AIT has high evidence of efficacy demonstrated by meta-analyses, and further improvement is currently apparent, as for diagnosis, applying the means of precision medicine. However, when AIT is performed in current practice, without the strict rules of controlled trials, long-term low adherence is a major problem to be solved.

Comparing the ability of molecular diagnosis and CAP-inhibition in identifying the really causative venom in patients with positive tests to Vespula and Polistes species.

BACKGROUND: Cross-reactivity among Hymenoptera venoms is an important issue when prescribing venom immunotherapy (VIT). Using all venoms eliciting a positive response results in treatment excess and unjustified cost increase. The first in vitro method that helped to identify the really causative venom was RAST-inhibition, but in latest years also molecular allergy (MA) diagnostics, that detects specific sIgE to single venom allergens, was introduced. We compared the two methods in patients with double sensitization to Vespula spp. and Polistes spp. METHODS: Fifty-four patients with anaphylactic reactions to Hymenoptera stings and positive results to skin tests and sIgE measurement with whole venom from Vespula spp. and Polistes dominula were included in the study. Sera from all patients were analyzed by CAP-inhibition (Thermo Fisher Scientific, Uppsala, Sweden) and MA diagnostics with recombinant Ves v 1, Ves v 5 and Pol d 5. RESULTS: By the data obtained from MA technique, VIT would have been prescribed to 7 patients for Polistes, to 6 for Vespula, and to 41 for both venoms. With the data from CAP inhibition, it would have been a prescription to 15 patients for Polistes, to 28 for Vespula, and to 11 for both venoms. A good concordance between the results of MA and CAP-inhibition was found only when the value in kU/l of Ves v 5 were about twice those of Pol d 5, and vice versa. CONCLUSIONS: These findings suggest that in the choice of the venom to be used for VIT CAP-inhibition remains a pivotal tool, because the significance of in vitro inhibition is definite and provides a diagnostic importance higher than MA in patients with positive tests to both Vespula and Polistes spp.

Risk of anaphylaxis in patients with large local reactions to hymenoptera stings: a retrospective and prospective study.

BACKGROUND: In the few studies available, the risk of developing systemic reactions (SR) to hymenoptera stings in patients with previous large local reactions (LLRs) to stings ranges from 0 to 7 %. We evaluated both retrospectively and prospectively the risk of SRs in patients with LLRs to stings. METHODS: An overall number of 477 patients, 396 with an SR as the first manifestation of allergy and 81 with a history of only LLRs after hymenoptera stings, were included in the study. All patients had clinical history and allergy testing (skin tests and/or specific IgE) indicative of allergy to venom of only one kind of Hymenoptera. Of the 81 patient with LLRs, 53 were followed-up for 3 years by annual control visits, while the 396 patients with SR were evaluated retrospectively. RESULTS: Among the 396 patients with an SR, only 17 (4.2 %) had had a previous LLR as debut of allergy, after an history of normal local reactions to Hymenoptera stings. All the 81 patients with a history of only LLRs had previously had at least two LLRs, with an overall number of 238 stings and no SR. Among the 53 patients who were prospectively evaluated we found that 31 of them (58.3 %) were restung by the same type of insect, with an overall number of 59 stings, presenting only LLRs and no SR. CONCLUSIONS: Our findings confirm that patients with repeated LLRs to stings had no risk of SR, while a single LLR does not exclude such risk. This has to be considered in the management of patients with LLRs.

Challenges in pulmonary rehabilitation: COVID-19 and beyond.

Pulmonary rehabilitation is a comprehensive multidisciplinary intervention requiring a team involving an expert chest physician, an exercise training specialist, a nutritional expert, a psychologist, a social worker, and an occupational therapist, who together aim at improving respiratory functional capacity in patients with chronic obstructive pulmonary disease (COPD). We aimed at evaluating the effectiveness of pulmonary rehabilitation in a large number of trials, systematic reviews, and meta­analyses in pre-COVID-19 conditions, and the impact of pulmonary rehabilitation during the COVID­19 pandemic was estimated based on results of abundant available studies. As many as 34 studies were selected to assess the global results of pulmonary rehabilitation in COPD patients before the pandemic, and 40 studies were selected from the literature concerning pulmonary rehabilitation during the COVID­19 pandemic.A large number of systematic reviews and meta­analyses reported on the efficacy of rehabilitation in COPD patients, based on the improvement in inspiratory muscle strength, exercise capacity, dyspnea, and quality of life. The response to rehabilitation in patients with COVID­19 is also satisfactory. The effectiveness of pulmonary rehabilitation in COPD patients shows an evolving need for health care professionals to design an individually tailored pulmonary rehabilitation program for patients with COVID-19 to alleviate the chronic symptoms and reduce complications.

Two decades with omalizumab: what we still have to learn.

From its availability for clinical use nearly two decades ago for severe asthma, omalizumab has gained strong evidence of efficacy and safety in the treatment of severe asthma not controlled by standard-of-care therapy. It has been acknowledged by Global Initiative on Asthma guidelines as add-on therapy against severe uncontrolled asthma. Thanks to controlled trials supporting its efficacy, omalizumab has also been licensed for the treatment of chronic spontaneous urticaria. The optimal duration of treatment in either disease has not been established. Despite its high price, omalizumab appears to be cost-effective in severe uncontrolled asthma as well as in chronic urticaria. The literature suggests a wide range of applications for omalizumab in various disorders regardless of allergic or non-allergic pathophysiology.

New combinations in the treatment of COPD: rationale for aclidinium-formoterol.

The current guidelines on chronic obstructive pulmonary disease (COPD) recommend the prominent use of bronchodilators, including long-acting ß2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), while inhaled corticosteroids are recommended only in patients with severe disease or frequent exacerbations. LABA-LAMA combinations are indicated when single bronchodilators are insufficient to control COPD. A number of LABA-LAMA combinations are available, based on twice-daily or once-daily administration according to the 12- or 24-hour duration of action, respectively. The aclidinium-formoterol combination is based on the new LAMA aclidinium bromide, which has a high selectivity for M3 muscarinic receptors and a fast onset of action, and the well-known LABA formoterol. Both drugs require twice-daily administration. The fixed-dose combination of aclidinium 400 µg/formoterol 12 µg has shown in randomized controlled trials fast and sustained bronchodilation that was greater than either monotherapy and provided clinically significant improvements in dyspnea and health status compared with placebo, also reducing the use of rescue medications. The overall incidence of adverse events was low and comparable to placebo. These data define the aclidinium-formoterol fixed-dose combination as a new treatment option for patients with COPD. The need for twice-daily administration could be an apparent disadvantage compared to the available once-daily LABA-LAMA combinations, but the immediately perceived benefit in reducing dyspnea due to the fast onset of action, as well as reported correct patient use and satisfaction with the Genuair inhaler might prove useful in favoring adherence.

Striving for optimal bronchodilation: focus on olodaterol.

ß2-agonists were introduced in the 1940s as bronchodilators to be used in obstructive respiratory diseases. Long-acting ß2-agonists have been a mainstay of bronchodilating treatment for decades. Recently, agents extending their effect to 24 hours and thus allowing the once-daily administration were introduced, defined as very-long-acting ß2-agonists. Olodaterol is a new very-long-acting ß2-agonist that has been shown, in controlled trials, to improve lung function as well as clinical outcomes and quality of life. Most of these trials included patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD). Olodaterol has a rapid onset of action (comparable to formoterol) and provides bronchodilation over 24 hours. In controlled trials, olodaterol was shown to be as effective as formoterol twice daily, but significantly superior in terms of quality of life in patients with COPD. The safety profile of olodaterol was very good, with a rate of adverse events, including the cardiac events that are particularly important for ß2-agonists, comparable to placebo. Also, the efficiency of the Respimat(®) device concurs to the effectiveness of treatment.

Pharmacodynamic and pharmacokinetic evaluation of house dust mite sublingually administered immunotherapy tablet in the treatment of asthma.

INTRODUCTION: Sublingual immunotherapy (SLIT) for house dust mite (HDM) allergy has an evidence of efficacy demonstrated by meta-analyses, but marked differences are reported between the various SLIT products. The standardized quality (SQ) HDM sublingual tablet containing Dermatophagoides pteronyssinus and Dermatophagoides farinae in a 1:1 ratio (MK-8237) is a qualitative advance for SLIT products. AREAS COVERED: The rationale for developing the HDM tablets is discussed against the other available SLIT products, analyzing the clinical data on efficacy and safety obtained by controlled trials. EXPERT OPINION: Following preliminary Phase I and II studies, a double-blind, placebo-controlled trial on 604 patients with mite-induced asthma, aged more than 14 years and treated by inhaled budesonide, was performed using one of three active doses (1, 3 or 6 SQ) or placebo. The results showed a significant mean difference between 6 SQ-HDM and placebo in the reduction in daily budesonide dose of 81 µg (p = 0.004), with relative mean and median reductions of 42 and 50% for 6 SQ-HDM and 15 and 25% for placebo, respectively. Safety was very good, with no report of anaphylactic reaction. These findings suggest a role to the HDM SLIT tablets in the treatment of patients with mite-induced asthma.