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Medical Journal Review

October 2021

WAO Reviews – Editors’ Choice

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

Advances and highlight in biomarkers of allergic diseases
Ogulur I, Pat Y, Ardicli O et al
Allergy 2021; Published online ahead of print (14-Sept)

Recent studies have demonstrated that allergic illnesses can largely be characterized by a type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable tools for precision medicine, as they provide information regarding disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network-based approaches, can help the identification of clinically useful biomarkers. The authors of this paper stress that these biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point-of-systems. Ideally, samples should be collected using quick, cost-efficient, and noninvasive methods. Promising biomarkers of type 2 allergic diseases include sputum eosinophils, serum periostin, and exhaled nitric oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body fluids, and exhaled air. In this review the authors examine recent studies on biomarkers for the diagnosis and treatment of asthma, chronic urticaria, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, anaphylaxis, drug hypersensitivity, and allergen immunotherapy. In addition, they discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.

Immune-mediated inflammatory disease therapeutics: Past, present and future
McInnes IB, Gravallese EM
Nature Reviews Immunology 2021;21:680-686

Immune- mediated inflammatory diseases are common and clinically diverse. Although presently these illnesses are incurable, the therapeutic armamentarium for immune-mediated inflammatory diseases has been transformed in the past two decades. As stressed by the authors, we have moved from the wide application of broad- spectrum immune modulators to the routine use of agents with exquisite specificity, arising from monoclonal and molecular biotechnology and more recently from highly targeted medicinal chemistry. In this article, Drs. McInnes and Gravallese explore key advances and lessons that drove this remarkable progress and thereafter reflect on the next steps in this ongoing journey.

Intolerance to angiotensin converting enzyme inhibitors in asthma and the general population: A UK population-based cohort study
Morales DR, Lipworth BJ, Donnan PT, Wang H
Journal of Allergy and Clinical Immunology: In Practice 2021;9(9):3431-3439.34

Angiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs, requiring switching to an angiotensin-II receptor blocker (ARB). It is believed that ACEI intolerance may be mediated by bradykinin, and thus may potentially affect airway hyperresponsiveness. To better understand this potential effect, Morales and colleagues assessed the risk for switching to ARBs in asthma through performing a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink, determining the risk for switching to ARBs in people with asthma or chronic obstructive pulmonary disease and the general population. They found that of 642,336 new users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR[1.16; 95% confidence interval [CI], 1.14-1.18; P £ .001) and highest in those at BTS step 3 or greater (HR [1.35, 95% CI, 1.32-1.39; and HR[1.18, 95% CI, 1.15-1.22, P £ .001 for patients aged ‡60 and <60 years, respectively). They found that the hazard was highest with enalapril (HR[1.25, 95% CI, 1.18-1.34, P £ .001; HR[1.44, 95% CI, 1.32-1.58, P £ .001 for BTS step 3 or greater asthma). Furthermore, they found no increased hazard was observed in chronic obstructive pulmonary disease or those younger than age 60 years at BTS step 1/2. The number needed to treat varied by age, sex, and body mass index (BMI), ranging between 21 and 4, and was lowest in older women with a BMI of 25 or greater.  Overall, they demonstrated that that ACEIs are less well tolerated in people with asthma compared with the general population. The NNT is lower in asthma and in those who are older age and female, and who have a higher BMI. The authors suggest that consideration could be given to recommending ARBs first in people with asthma or those with high-risk characteristics when treatment with a renin-angiotensin system inhibitor is clinically indicated.

The applications of eHeath technologies in the management of asthma and allergic diseases
Alvarez-Perea A, Dimov V, Popescu FD et al
Clinical and Translational Allergy 2021;11(7):e12061 (6-Sept)

In this review, Alvarez-Perea and colleagues review the literature regarding eHealth. They note that through the use of this technology, clinicians and patients have been given the opportunity to communicate in new and more cost-effective ways. Furthermore, through the use of this technology, new research opportunities have arisen. As pointed out by the authors, the role of eHealth has become more important since the onset of COVID 19 with resultant restrictions. These tools are here to stay, but require continued evaluation to optimize their use. 

Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy
Shamji MH, Larson D, Eifan A et al
Journal of Allergy and Clinical Immunology 2021;148(4):1061-1071.e11 (1-Oct)

There are no detailed comparisons of allergen specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). In this study, Shamji and colleagues compared nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT, as well as 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively. They found that at years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P < .01). TGPIgA1 level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P < .001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG4 level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P < .01). Serum IgG4 levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9- fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P <.05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P =.04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG4 to TGP components stratified participants according to treatment group and clinical response. These results indicate that production of IgA is a major biological difference between SLIT and SCIT. Although, as expected, SCIT induced higher specific IgG4 levels than SLIT, SLIT led to higher IgA levels, both in serum and in nasal fluid. Furthermore, the levels of IgA1 in nasal fluids correlated with SLIT’s suppression of nasal symptoms during NAC. The authors opine that specific IgA antibody production may represent a distinct mechanism through which SLIT exerts its therapeutic effects.


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