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Medical Journal Review

January 2022

WAO Reviews – Editors' Choice

Articles are selected for their importance to clinicians who care for patients with asthma and allergic and immunologic diseases by WAO Reviews Editors Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD, FACAAI, FAAAAI.

Regulated on Activation, NormalT cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma
Li N, Mirzakhani H, Kiefer A et al
iScience 2021;24(10):103163 (24 September)

Regulated on Activation, NormalT cell Expressed and Secreted (RANTES) has been implicated in allergic asthma and in T cell-dependent clearance of infection. The RANTES receptor family includes CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses result in the induction of RANTES production by epithelial cells. In this study, the authors explored the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma, extending this study by examining the airways of adults with and without asthma and finally translating these results to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Through these studies, they found an unpredicted therapeutic role of RANTES in the actual resolution of allergen-induced asthma, presumed through orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung.

The majority of children sensitized before school age develop allergic disease before adulthood: A longitudinal population=based study
Bunne J, Hedman L, Perzanowski M et al
Journal of Allergy and Clinical Immunology: In Practice 2021; Published online ahead of print (22 October)

While it is known that allergic sensitization increases the risk of and asthma and allergic rhinitis, the impact of age at onset of sensitization has been less studied. To understand this relationship better, the authors examined the cumulative incidence of asthma and rhinitis up to age 19 years in relation to age at onset of sensitization to airborne allergens. To do so, they invited all children in grades one and two (median age 8 years) in two municipalities in Northern Sweden to undergo skin prick tests and perform a questionnaire regarding allergic diseases (88% participated). At ages 12 and 19 years the protocol was repeated, with n=1510 individuals participating in all three examinations. Specific IgE was collected in a random sample at age 19, n=770. The authors stratified age of onset of sensitization to: ≤8 years, 8-12 years, 12-19 years, and never sensitized, finding that at age 19, those sensitized ≤8 year had the highest risk of asthma (RR 4.68 (95%CI 3.14- 66 6.97) and rhinitis (RR 22.3 (95%CI 13.3-37.6), with 84% had developing either asthma or rhinitis. They furthermore found that the combination of sensitization ≤8 year and family history of allergic diseases rendered high risks for asthma (RR 10.6 [6.71-16.7]) and rhinitis (RR 36.3 [18.9-69.7]). Individuals sensitized ≤8 year showed the significantly highest level of sensitization, as judged by number of positive skin tests and titers of specific IgE.

Psychological impacts of COVID-19 on people with asthma, allergic rhinitis and food allergy
Burrows AG, Ellis AK
Annals of Allergy Asthma and Immunology 2021; Published online ahead of print (28 December)

In this paper, Drs. Burrows and Ellis examine the psychological Impact of COVID-19 on people with allergic illness, finding that asthma patients perceived their risk of severe disease from COVID-19 as greater, which negatively impacted their psychological wellbeing. Presently, there are only limited data regarding the impact of COVID-19 in allergic rhinitis (AR) and food allergy (FA) patients; however, it has been found that some AR patients experienced high anxiety and depression compared to healthy controls. Parents and caregivers of children with asthma and FA were also affected with a higher psychological burden during COVID-19. The authors note that it is important that physicians be aware of the potential coincidence of mental illness and chronic allergic diseases, and refer these patients, and their caregivers, to appropriate resources, while also continuing to manage their allergic disease(s).

Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study
Fritzsching B, Contoli M, Porsbjerg C et al
Lancet Regional Health – Europe 2021;13:100275 (30 November)

While a multitude of studies has demonstrated the efficacy of allergen immunotherapy (AIT), the long-term, real-life effectiveness of AIT has not been as well studied. To resolve this issue, the REACT (Real world effectiveness in allergy immunotherapy) was performed.  REACT was a retrospective cohort study using claims data between 2007 and 2017 in patients with a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analyzed both as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up. There were 46,024 AIT-treated subjects matched with control subjects, and 14,614 were included in the pre-existing asthma cohort. They found that compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in both AR as well as asthma prescriptions (both asthma controller and reliever prescriptions). Additionally, the AIT group had a significantly greater likelihood of stepping down asthma treatment (P <0.0001) as well as a demonstrated reduction in severe asthma exacerbations (P<0.05).  They also found reductions in pneumonia with antibiotic prescriptions, hospitalizations, and duration of inpatient stays in the group on AIT. Overall, this study extends the existing RCT evidence for AIT, demonstrating long-term and sustained effectiveness of AIT in the real world, with an associated reduced likelihood of asthma exacerbation or pneumonia in patients with concurrent asthma.

Clinicopathological characteristics of IgG4-related lung disease
Liu J, Liu Y, Shen X et al
BMC Pulmonary Medicine 2021; 21(1):413 (15 December)DOI:

Immunoglobulin G4-related lung disease (IgG4-RLD) is a rare entity. To improve upon our ability to diagnose this illness, the authors retrospectively analyzed the clinical and histopathological characteristics of patients with pathologically confirmed IgG4-RLD. From a group of 4838 patients seen in their facility with pulmonary biopsy results, they found 65 patients with suspected IgG4-RLD, of whom analysis of these 10 patients revealed an average age of 59.7 years at diagnosis, and a male-to-female ratio was 9:1. The initial clinical manifestations were nonspecific, with cough being the most common symptom (4/10). More than one organ was involved in most patients (8/10), and mediastinal/hilar lymph node involvement was often observed (7/10). Serum IgG4 was analyzed in 6 patients and found to be elevated. Computed tomography (CT) of the chest and/or 18F-fuorodeoxyglucose positron emission tomography-computed tomography imaging revealed that 5 patients had a mixed type, 3 patients had the solid nodular type, and 2 patients had the bronchovascular type. All pulmonary masses and large nodules with solid patterns had spiculated margins and inhomogeneous enhancement with or without pleural indentation and a lobulated appearance. Abundant lymphoplasmacytic cell infiltration and fibrosis were observed in all patients. The expression of IgG4 and IgG was upregulated in the pulmonary sections. Seven patients were treated with glucocorticoids with or without additional immunosuppressants and responded well.

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