Medical Journal Review
May 2022
WAO Reviews – Editors' Choice
The WAO Reviews editors, Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, select articles on a monthly basis for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases.
Asthma remission – What is it and how can it be achieved?
Thomas D, McDonald VM, Pavord ID, Gibson PG
European Respiratory Journal 2022; Published online ahead of print (31 March)
https://doi.org/10.1183/13993003.02583-2021
Currently, asthma treatment goals focus on symptom and exacerbation control rather than remission. This review explores the current definitions of remission in asthma, the prevalence and predictors, pathophysiology of remission, possibility of achieving remission via using the available treatment options, and future research directions. Asthma remission is described as a high level of disease control (including the absence of symptoms and exacerbations), with normalization or optimization of lung function with or without ongoing treatment. The authors point out that even in patients who achieve a symptomatic remission of their asthma, persistent pathological abnormalities are common, leading to a risk of subsequent relapse at any time. Therefore, complete remission requires normalization or stabilization of any underlying pathology beyond symptomatic remission. It should be noted that remission can occur as part of the natural history of asthma, with the reported prevalence of remission in the adult asthma population varying between 2% and 52%. Factors associated with remission include: mild asthma, better lung function, better asthma control, younger age, early-onset asthma, shorter duration of asthma, milder bronchial hyper-responsiveness, fewer comorbidities, and smoking cessation or never smoking. Although previous studies have not targeted treatment-induced remission, there is some evidence to show that the current long-term add on therapies such as biologics and azithromycin can achieve some criteria for asthma remission on treatment, at least in a subgroup of patients. Certainly, more research is needed, as remission is our ultimate goal.
Characterization of asthma by age of onset, a multi-database cohort study
Baan EJ, de Roos EW, Engelkes M et al
Journal of Allergy and Clinical Immunology: In Practice 2022; Preproof
https://doi.org/10.1016/j.jaip.2022.03.019
While the onset of asthma can occur at any age, the differences in patient characteristics between childhood-, adult-, and late-onset asthma are not well understood. Thus, in this study Baan and colleagues investigated patient characteristics by age at asthma onset, through mining European electronic data. They categorized patients based on their age at asthma onset: childhood-onset (age at onset < 18 years), adult-onset (age at onset 18-40 years) and late-onset asthma (age at onset >=40 years). Comorbidities were assessed at study entry. For each characteristic and comorbidity, odds ratios (OR) and age- and sex-adjusted OR(ORadj) comparing asthma onset categories were estimated per database and combined in a meta-analysis using a random effect model. They found that patients with adult onset compared to childhood-asthma had higher risk of being overweight/obese (ORadj 1.4, 95%CI 1.1- 1.8) and lower risk of having atopic disorders (ORadj 0.8, 95% CI 0.7-0.95). Patients with late-onset compared to adult-onset asthma had higher risk of nasal polyposis (ORadj 1.8, 95%CI 1.2-2.6), overweight/obesity (ORadj 1.3, 95%CI 1.2-1.4), gastro-oesophageal reflux disease (ORadj 1.4, 95%CI 1.2-1.7) and diabetes (ORadj 2.3, 95%CI 1.8-2.9). They also found a significant association between late-onset asthma and uncontrolled asthma (ORadj 2.8, 95%CI 1.7-4.5)). Overall, this study demonstrates clear differences in comorbidities between childhood-, adult-, and late-onset asthma phenotypes in adults.\
Short-acting β2-agonist exposure and severe asthma exacerbations: SABINA findings from Europe and North America
Quint JK, Arnetorp S, Kocks JWH et al
Journal of Allergy and Clinical Immunology: In Practice 2022; Preproof
https://doi.org/10.1016/j.jaip.2022.02.047
Expert national/global asthma management recommendations raise the issue of whether a safe threshold exists of short-acting β2-agonist (SABA) use without concomitant inhaled corticosteroids (ICS). To answer this question, Quint and colleagues examined SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe via observational analyses of 10 SABa use IN Asthma (SABINA) datasets which included 1,033,564 patients (≥12 years) from around the world. They found that across severities, 40.2% of patients were prescribed/possessed ≥3 SABA canisters/year. Per GINA-2018 definitions, step 3‒5-treated patients prescribed/possessing ≥3 vs. 1‒2 SABA experienced more severe exacerbations (between 1.08 [1.04‒1.13], US-Medicare; 2.11 [1.96‒2.27], Poland). This association was not observed in all step 1‒2-treated patients (the Netherlands 1.25 [0.91‒1.71]; US-commercial 0.92 [0.91‒0.93]; US-Medicare 0.74 [0.71‒0.76]). The authors suggest that this inverse association between SABA and severe exacerbations in the US datasets was the large patient population possessing <3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face healthcare provider encounters. In US SABA monotherapy-treated patients, ≥3 SABA was associated with more emergency/outpatient visits and hospitalizations (1.31 [1.29‒1.34]). Most GINA 2‒5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of ≥3 SABA and severe exacerbations persisted (1.32 [1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when the UK SABA data was analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. This study demonstrates that increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy and reinforces the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.
Characteristics of exogenous allergen in breast milk and their impact on oral tolerance induction
Kosmeri C, Rallis D, Kostara M et al
Frontiers in Pediatrics 2022; 830718 (4 March)
https://doi.org/10.3389/fped.2022.830718
In light of the rising prevalence of food allergies, many have focused on ways to diminish this trend – including the consideration of breast feeding as a modality to induce oral tolerance. This review summarized the evidence from experimental and human studies regarding allergen characterization of human breast milk that may influence oral tolerance induction. Studies demonstrate that the dose of antigen in human milk is in the range of nanograms/ml. The authors point out that the presence of antigen-specific immunoglobulins, forming immune complexes with antigens, has been reported to be more tolerogenic compared with free allergens. This articles also provides a great discussion regarding gaps in our present knowledge.
Food protein-induced enterocolitis syndrome: A large French multicentric experience
Lemoine A, Colas AS, Le S et al
Clinical and Translational Allergy 2022;12(2):312112 (17 February)
https://doi.org/10.1002/clt2.12112
There is concern that variability may exist regarding culprit foods, and age of tolerance in food protein-induced enterocolitis syndrome (FPIES) depending on the country of origin. In this study, the authors explore the characteristics of a French population of children with FPIES and define risk factors for failure during challenge through retrospective evaluation of children from two French pediatric tertiary centers with a diagnosis of FPIES (based on international consensus guidelines). In the 192 described FPIES patients, the age at first symptoms was 5.8 months old with the main offending foods being cow's milk (60.3%), hen's egg (16.2%), and fish (11.7%). Single FPIES was observed in 94.4% and multiple FPIES in 5.6% of cases. The age at resolution of FPIES was 2.2 years old, and resolution occurred later for fish than for milk (2.9 years vs. 2.0, p = 0.01). Severe acute FPIES was a risk factor for delayed resolution (RR: 3.3 [1.2–9.2]), but not IgE sensitization.
