This session discussed abstracts on the various biomarkers, diagnostic techniques, and novel allergy, asthma, and COPD treatment interventions.
Patients with rhinitis to pollen may develop asthma. Face masks have become widely used around the world to help control the spread of SARS-CoV-2. However, there is no clinical evidence that medical masks are more effective in asthma caused by birch pollen. A study investigated the efficacy of medical face masks in reducing asthma in patients allergic to birch in the ALYATEC Environmental Exposure Chamber (EEC). The Kaplan-Meyer graph revealed that the group with masks had a higher survival probability in EEC than the group without masks. The study demonstrated a tendency of face masks to increase the time of asthma development. Some patients reported that the mask was effective during the pollen season.
Allergic rhinoconjunctivitis is mainly induced by birch pollen. There is a significant disparity between patient-reported asthma and responses to bronchial allergen challenges. A study was conducted to investigate asthma responses to birch allergen in patients with and without asthma in the ALYATEC Environmental Exposure Chamber (EEC). In patients with AR without asthma, 53.3% of patients had early asthma response (EAR), and 16.6% of patients had late asthma response (LAR). The average time to obtain EAR was 77 minutes. Dual asthmatic responses were more common in patients with early nasal responses. In all asthmatics, EAR occurred within 34 minutes, followed by 62.5% of LAR. Birch-related asthma appears to be underestimated in AR patients. In more than 50% of asthmatics, birch allergen-induced dual bronchial responses. These findings are comparable to those obtained in mite asthmatics, implying that birch is as asthmogenic as mite allergen.
Clinical trials of COVID-19 vaccination show evidence of side effects in the placebo group, which is consistent with some reported side effects being a placebo effects. This study aimed to determine whether side effects of COVID-19 vaccination are associated with negative vaccination beliefs. Patients with severe asthma reporting severe side effects had significantly more mistrust of vaccine efficacy, more concerns about future effects and profiteering but not significantly more preference for natural immunity. The study findings suggested that negative beliefs create negative expectations and side effects.
Respiratory allergy frequently affects the upper and lower airways as allergic rhinitis (AR) and asthma, increasing the risk of asthma exacerbations and pneumonia. Allergy immunotherapy (AIT) administered as the SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-the tablet has shown efficacy in adults for both AR and asthma. However, long-term data for AIT in asthma are limited. In subjects with AR and pre-existing asthma, AIT was associated with a higher likelihood of stepping down in asthma controller treatment and a lower risk of asthma exacerbations and pneumonia. Across all years, except year 3, the odds ratios (OR) for a step-up in asthma controller treatment were lower in the AIT group compared to controls. In addition, lower ORs for antibiotic use supported the reduced risk of pneumonia in all years except year 8, reaching significance in years 1-3, 5, and 6. These findings support that AIT may lower the risk of asthma severity progression and lower airway infections.
Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high symptom burden. The SINUS-52 study demonstrated the efficacy of dupilumab in CRSwNP; dupilumab was also well tolerated. Therefore, the SINUS-52 study aimed to characterize the efficacy of dupilumab in terms of onset, maintenance, and durability of individual response. Among dupilumab-treated patients who responded by week 16, >82% for nasal polyp score (NPS), >87% for loss of smell score (LoS), and >86% for 22- item Sino-Nasal Outcome Test (SNOT-22) maintained responses at week 52. In addition, more patients with dupilumab achieved clinically relevant response (onset) than placebo by week 16, with the response maintained at week 52 in >82% of dupilumab patients.
Omalizumab has been approved to treat severe allergic asthma. However, not all patients benefit from this treatment. IgE is an essential component of allergic inflammation, and total IgE levels in serum and saliva were found to correlate. The study's objective was to check if salivary IgE levels may be used as a non-invasive marker of disease severity in asthmatics treated with omalizumab. Total IgE in saliva was linked to FEV1 and FVC in severe asthmatics, making it a potential marker for monitoring the outcomes of IgE-targeting therapy.
Vaccination has emerged as a critical tool in the fight against COVID-19. ORF1ab (open reading frame1ab) is the largest ORF of the SARS-CoV-2 genome. Furthermore, the ORF1ab protein is translated early in infected cells. Besides, ORF1ab is genetically stable and may be a valuable source of conserved epitopes appropriate to prepare effective protein vaccines for the control of many SARS-CoV-2 variants. Numerous studies have found hypersensitivity responses to SARS-CoV-2 vaccines. In the study, SARS-CoV-2 ORF1ab protein allergenicity was predicted by bioinformatics. ORF1ab protein of SARS-CoV-2 was demonstrated to be an allergen, as confirmed by allergen FP server V.1. ORF1ab protein, a valuable source of conserved epitopes, is suitable for the development of effective protein vaccines for the control of many SARS-CoV-2 variants. Recognizing and eliminating the allergenic epitope (s) is required to prepare safe and effective anti-SARS-CoV-2 vaccines from ORF1ab protein.
Patients with severe asthma (SA) may be at higher risk of developing severe COVID-19. COVID-19 vaccines aim to lower the number and severity of infections. Patients with SA are frequently treated with oral maintenance corticosteroids (mOCS) and/or biologics (mAb); it is unknown whether the COVID-19 vaccine will produce the same protective responses in patients with SA as other therapies. A study compared the magnitude and range of post-vaccination (PV) antibody responses (IgG) in patients with SA on mAb, mOCS, or high-dose inhaled corticosteroids (ICS) with healthy controls (HC) without asthma. After receiving two doses of a COVID-19 vaccine, a higher proportion of patients with SA had a negative PV IgG level. This was most noticeable in patients receiving mOCS, whereas mAb use was associated with a high level of humoral antibody response. These findings highlight the importance of booster vaccines in SA, particularly for those on mOCS.
Patients with moderate-to-severe asthma may be at risk of accelerated decline in lung function (LFD). There are currently few prognostic and predictive biomarkers for LFD. Dupilumab (DPL) treatment may help to prevent LFD. In phase 3 QUEST, DPL demonstrated an acceptable safety profile. A study aimed to understand baseline characteristics associated with rapid LFD in QUEST placebo (PBO) patients and the effect of DPL on LFD across biomarker levels. FeNO was higher in patients with rapid LFD than in those without decline. In addition, FeNO demonstrated a more significant slope difference between DPL and PBO in populations with a higher baseline, implying that FeNO may be prognostic for LFD and predictive of DPL response.
Asthma with chronic rhinosinusitis with nasal polyps (CRSwNP) has a higher burden and more complex treatment. Therefore, a multidisciplinary team of ENT physicians, allergologists, pneumologists, and hospital pharmacists set out to create a patient assessment checklist based on the diagnostic definition and control and severity criteria established in guidelines such as GINA, ARIA, EPOS, and international consensus on biologic therapies for CRSwNP and Asthma from EUFOREA and EAACI, as well as a multidisciplinary consensus-based 4-step diagnostic algorithm SEPAR. Defining phenotypes and endotypes were the focus of the discussion. A final checklist of 17 items was agreed upon for a common approach. This 17-item checklist is intended to aid in the standardization of an interdisciplinary approach for managing severe asthma and CRSwNP, as well as in the decision to biological therapy.
Hospitalizations and emergency department (ED) visits in patients with chronic obstructive pulmonary disease (COPD) impose a significant healthcare burden. Itepekimab is a novel human IgG4P monoclonal antibody against interleukin-33. A recent phase 2 study showed that itepekimab 300 mg every two weeks reduced exacerbation rates and improved lung function compared to placebo in a subgroup of former smokers with moderate-to-severe COPD over a 24-52-week treatment period. This post hoc analysis of the phase 2 study investigated the effect of itepekimab compared to placebo on hospitalizations and ED visits in former smokers with COPD. In former smokers with moderate-to-severe COPD, itepekimab significantly reduced hospitalizations or ED visits compared to placebo. In addition, former smokers treated with itepekimab had a 70% lower risk of hospitalization or ED visit and a longer time to first hospitalization or ED visit when compared to placebo.
Respiratory allergy often affects the upper and lower airways as allergic rhinitis (AR) and asthma, negatively impacting sleep. Allergy immunotherapy (AIT), particularly for house dust mite (HDM) allergy, has been shown to be an effective asthma treatment. However, long-term data on AIT in asthma and sleep are limited. The real-world effectiveness of the AIT (REACT)-study was a large, retrospective German cohort study with a follow-up of up to 9 years. In patients with AR and pre-existing asthma, AIT was associated with long-term improved asthma control, as well as a lower risk of asthma exacerbations and hospitalizations. This study investigated the effect of AIT on sleep disturbances in the cohort with AR and pre-existing asthma. In all nine years of follow-up, AIT-treated patients had a lower prevalence of sleep disturbances than controls. The prevalence was stable in the AIT group, but the prevalence appeared to increase over time for controls. The results support the long-term efficacy of AIT in patients with AR and concomitant asthma.
Dupilumab (DPL), a fully human anti-IL-4R mAb, inhibits interleukin-4/13, one of the most critical and central drivers of type 2 inflammation. TRAVERSE, a single-arm, open-label extension study, assessed the long-term safety and efficacy of DPL 300mg once every two weeks for up to 96 weeks in patients from VENTURE. The study aimed to evaluate DPL efficacy in TRAVERSE patients with severe OCS-dependent asthma by OCS dose at the parent study baseline. The study demonstrated that OCS dose reductions were sustained. In addition, improvements in AER and lung function continued during TRAVERSE.
Zingiber cassumunar Roxb. (Phlai) has been used for the treatment of inflammation and chronic airway diseases in traditional Thai medicine based on active constituent compound D, showing potential antiallergic and anti-inflammatory effects. From a multicenter trial, the effects of Phlai on patient-reported AR symptoms and their safety were reported. At week 4, patients who received active treatments had significantly greater relief from a total five symptom score (T5SS), rhinorrhea, itchy nose (IN), and itchy eyes (IE) symptoms than those who received placebo. Phlai was well tolerated with no severe side effects. In patients with AR, Phlai capsules may be used as an adjunct treatment to alleviate symptoms such as rhinorrhea, IN, and IE.
Tozorakimab (MEDI3506) is a human monoclonal antibody that targets interleukin (IL)-33, a cytokine that plays a vital role in inflammatory disease. Tozorakimab is being tested in clinical trials for various conditions, including COPD. A study was conducted to build a mechanistic population pharmacokinetic (PK)/pharmacodynamic (PD) model for tozorakimab, using the phase 1 systemic target engagement biomarker data to enable dose selection for future studies. The PK/PD model accurately predicted systemic and pulmonary target engagement by tozorakimab. In future clinical trials, the model will aid in determining optimal tozorakimab dosing.
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a vasculitis characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy and multiorgan eosinophilic vasculitis. Eosinophils play a critical pathogenic role in EGPA. Some evidence supports the use of Benralizumab (BZ), a humanized monoclonal antibody that binds interleukin-5 receptors and is approved for severe asthma. A study assessed BZ treatment in patients with EGPA and severe asthma for 1 year. One year after the first administration, improvement in FEV1 and complete depletion of blood eosinophilia were observed. Benralizumab appears to affect not only peripheral blood eosinophilia but also antineutrophil cytoplasmic antibodies (ANCAs) production and oral corticosteroids (OCS) requirements, thus preventing organ damage, improving respiratory function, and quality of life.
Adults with chronic respiratory disorders have a higher risk of pertussis. Therefore, a study was conducted to determine whether the immunogenicity and safety of the diphtheria-tetanus-pertussis vaccine (dTap) are impacted by obstructive airway disease (OAD) treatment. The study showed that OAD treatment did not impact the immunogenicity and safety of adult dTap vaccination compared to general population data. Thus, adults treated for OADs demonstrated adequate seroprotection, immune response rates and tolerability to dTap.
TRAVERSE evaluated the long-term safety and efficacy of dupilumab (DPL) in patients aged ≥12 years who had previously completed a DPL asthma study. This study evaluated the long-term effects of DPL on asthma control (ACQ-5 score) and health-related quality of life (HRQoL; AQLQ score) up to 48 weeks, as well as annualized sick leave days due to severe exacerbations (AER). The study concluded that in patients with moderate-to-severe type 2 asthma, DPL was associated with sustained improvements in asthma control over a 48-week treatment period and less than one sick leave day per year (annualized rate) due to AER.
European Respiratory Society (ERS) International Congress 2022, 3rd-6th Sept. 2022, Barcelona
