Documents from the SIAIP Commissions

Issue 3 - 2024

Alternatives to the allergen- specific nasal provocation test: role of molecular allergens for grasses in poly-sensitized children with seasonal allergic rhinitis

Authors

SIAIP New Digital Technologies Commission , Mario Barreto , Auro Della Giustina , Ifigenia Sfika , Stefano Pattini , Alessandro Travaglini , Maria Antonia Brighetti , Denise De Franco , Alessandro Di Menno Di Bucchianico , Velia Malizia , Salvatore Tripodi

Key words: Allergic rhinitis, AllergyMonitor, nasal provocation test, grass pollens, polysensitized children
DOI: 10.53151/2531-3916/2024-564
Publication Date: 2024-10-07

Abstract

Allergic rhinitis (AR) affects 10-30% of the global population, notably children and adolescents, leading to reduced quality of life and comorbidities like asthma. An Italian multicenter study indicated that 85% of children tested positive for multiple pollen allergens, with Timothy grass predominant. IgE antibodies against Phleum Pratense, Bermuda grass, olive, and cypress are highly prevalent in southern Europe, where overlapping pollination periods complicate the identification of specific seasonal allergens in poly-sensitized patients. For some patients, allergen-specific immunotherapy is necessary when symptomatic therapy is insufficient. Molecular diagnostics and nasal provocation testing (NPT) are crucial to identify relevant allergens. NPT remains the gold standard for documenting clinical relevance in seasonal AR, but is challenging in poly-sensitized children. Non-invasive strategies, e-Diary for symptoms, and IgE-specific activity analysis are being explored. This summary reviews the predictive value of clinical and biological data for NPT outcomes in pediatric patients co-sensitized to grasses and other seasonal pollens. Clinical data assessed with the visual analogue scale can predict NPT outcomes. Biological data, including specific IgE levels and skin prick tests, have shown varying predictive values. Combining clinical scores and biological markers, such as IgE-specific activity for grass-pollen molecules, enhances prediction accuracy for positive NPT outcomes

Article

Allergic rhinitis (AR) impacts approximately 10-30% of the world’s population, especially children and adolescents; ocular-nasal, systemic symptoms and those secondary to therapies characterize it. The most severe symptoms are associated with reduced quality of life, school absenteeism, outdoor sports limitations, and comorbidities such as asthma 1,2.

Data from an Italian multicenter study revealed that nearly 85% of children tested positive for at least 3 allergens, with Timothy grass being the dominant allergen in about 90% of cases 3. Recently, a high prevalence of IgE antibodies against major molecules from Phleum Pratense (Phl p 1 and Phl p 5), Bermuda grass (Cyn d 1), olive (Ole 1), and cypress (Cup A 1) was described in 9 centers across southern Europe. The distribution was more heterogeneous for other pollen molecules, and variability was observed in pollen sensitization profiles and clinical manifestations 4.

Poly-sensitization makes it challenging to identify the specific allergen responsible for AR symptoms during the pollen season 5. Even when aerobiological data are available to assess the correlation between symptoms and pollen concentrations, the difficulty is exacerbated by overlapping pollination periods, especially in southern European regions 4,6. In contrast, central-northern areas exhibit more sequential pollination periods for grasses and other pollens (e.g., birch) 4.

For some patients, symptomatic therapy alone is insufficient to control the severity of seasonal rhinitis, necessitating allergen-specific immunotherapy (AIT) 5. Molecular diagnostics (CRD) allows the identification of the most relevant allergenic molecules and optimizing AIT prescription 7. Other patients do not show a serum sensitization profile corresponding to the local, causal symptoms, and nasal provocation testing (NPT) is necessary 2, 8.

NPT remains the ‘gold standard’ for documenting the clinical relevance of a specific allergen in patients with seasonal AR 8. However, choosing the appropriate allergen is challenging in patients who are poly-sensitized to pollens, and performing the NPT can be cumbersome in children. Additionally, execution of the NPT requires standardizing environmental and procedural conditions, and clinical-therapeutic patient monitoring 8,9.

An alternative non-invasive strategy to NPT can be studied using algorithms that incorporate quantitative and semi-quantitative parameters, including digital symptom assessment technologies and analysis of IgE-specific activity for grass-pollen molecules as their percentage fraction from total IgE 10.

This summary outlines experiences from various studies regarding the predictive value of clinical and biological data for NPT outcomes. Specifically, it discusses the diagnostic value of NPT surrogates in pediatric patients who are co-sensitized to grasses and other seasonal pollens, whose severe AR symptoms justify AIT prescription.

PREDICTIVE PARAMETERS FOR A POSITIVE NPT OUTCOME

Clinical Data

There are various semi-quantitative methods for retrospective or prospective self-assessment of symptoms related to pollen seasons. These methods help guide pharmacological therapy and evaluate the effectiveness of allergen immunotherapy (AIT) 7,9,11. However, studies on the value of psychometric scales in predicting a positive response to NPT for grasses remain scarce 12,13. The development of apps such as MASK or AllergyMonitor has made patient follow-up easier through an “e-diary” 14,15. Within the “AllergyMonitor” app (AM) (TPS Production, Rome, Italy), three self-assessment methods — the “Rhinoconjunctivitis Total Symptoms Score” (RTSS, 0-18), the “Combined Symptom and Medication Score” (CSMS, 0-6), and the “Visual Analogue Scale” (VAS, 0-10) — allow patients to enter detailed scores for nasal and ocular symptoms as well as medication use (RTSS, CSMS) and assess their clinical progress (VAS) daily 15-20.

The VAS is a psychometric scale that is considered simple to use and well correlated to the ARIA criteria 21. This scale can be applied to rate the severity of each AR symptom (e.g., nasal obstruction, runny nose, itching, sneezing) or the overall symptoms’ severity by asking: “How much did your allergy symptoms bother you today?”. In addition to monitoring, VAS is useful for assessing the total symptoms’ severity relating to the previous pollen season.

Recently, in allergen poly-sensitized pediatric patients with AR, we have found that clinical VAS scores (overall symptoms) assessed daily and those referring to the previous pollen season were comparably useful in predicting the NPT outcome 13. A close relationship between the e-diary and retrospective ARIA data has been previously reported 22. Patient data of the AM App were analyzed as maximum values and coefficients of variation (CV=100* SD/mean) for RTSS, CSMS, and VAS during days with high pollen concentrations (>30/m3) following the EAACI criteria 23,24. VAS (AM), but not RTSS or CSMS, was predictive of NPT outcome; VAS maximum value: sensitivity (Se) 72.1%, specificity (Sp) 63.6%; VAS CV%: Se 80.3%, Sp 63.6%. Furthermore, the overall VAS on the previous pollen season (retrospective) showed a modest Se (60.7%) and good Sp (81.8%) for a positive NPT.

In contrast to our results, a prior study in adult patients found no relationship between the VAS referring to the previous pollen season and the outcome of NPT titrated to increasing concentrations of grass extract 12. Of note, we performed the NPT with an undiluted extract, more suitable for clinical use, as per current international guidelines 8.

Biological data

Biological data considered for AIT include skin prick tests (SPT), specific serum IgE, and more recently, CRD 5,7,25. The substitutive value of biological data to NPT has been the subject of numerous studies. Regarding SPT positivity (defined differently by individual studies), a recent meta-analysis of 7 studies on various airborne allergens described pooled sensitivity and specificity of 70% and 86% respectively 26; three of these studies reported dissimilar values (sensitivity between 68-97% and specificity between 70-86%) for the positive response to NPT with Timothy grass extract 27-29. The extent of allergic sensitization understood as the wheals’ size or the specific IgE levels, has also been reported to be predictive for the NPT outcome to various inhalant allergens (Dpt, cat, Salsola K. pollen) 30-34. On the other hand, the diameter of the skin reaction to Timothy grass was not shown to be predictive of NPT, but only the cut-off (0.35 kUA/L) for specific IgE to the same allergen 35.

A study in 101 adult patients evaluated serum IgE against eight Phleum pratense molecules (Phl p: 1, 2, 4, 5b, 6, 7, 11, and 12); the authors found that increased numbers of sensitizations exceeding the cut-off 0.35 kUA/L predicted NPT and conjunctival challenge positive results 36. From our recent study in 72 poly-sensitized children, only serum Phl p 5 concentrations ≥ 0.35 kUA/L were common in NPT-positive patients (64% vs 18.2% in TPN-negatives); instead, Phl p 1 and Phl p 4 were equally frequent and others (Phl p 7 and Phl p 12) were infrequent in both groups examined 13. This is consistent with the recognized allergenic capacity of Phl p 5, attributable to the numerous epitopes of this molecule 37, as well as the high risk of developing asthma in patients who are sensitized to it 38.

A few years ago, quantification of IgE-specific activity for a given allergen was proposed 10. This approach calculates for each specific IgE its percentage of total serum IgE, i.e., (specific IgE/total IgE) *100 39. The index provides an estimate of the degree of allergic sensitization and, ultimately, the clinical impact on the patient; this approach has proven useful to evaluate the development of tolerance in food allergies and the effectiveness of AIT 40, 41. IgE-specific activity is part of the parameters of the humoral immune response that act in the release of mediators from mast cells and basophils, together with IgE concentrations, affinity, and heterogeneity in specific epitopes of the antibody 42.

We hypothesized that the measurement of the serum IgE-specific activity for grasses is a useful tool to improve the predictive capacity of the response to NPT. For the challenge, the allergenic extract Graminacee blend, 300 SRU/ml (ALK Abellò - Milan, Italy), which has an allergen concentration of Phl p 5 equal to 26 mcg/ml, was administered 13. We estimated the predictive value of specific IgE for Phleum pratense and Bermuda grass and the molecules Phl p 5 and Cyn d 1 and their IgE-specific activity in determining a positive NPT result. The IgE-specific activities for each of these molecules were found to be more predictive of the NPT outcome than the IgE-specific activities for Phleum and Bermuda, also compared to the diameter of the SPT wheal reactions for the two allergens. The combined IgE-specific activity for both molecules, i.e., (specific IgE for Phl p 5+Cyn d 1/total IgE)*100, reached the highest predictive value for TPN outcome; for a cut-off ≥ 7.25%: Se 70.5%, Sp 90.9% 13.

Clinical-biological algorithms

From what has been stated, it appears possible to identify pediatric patients who are candidates for AIT without resorting to NPT. Combining clinical scores (prospective and retrospective) and biological biomarkers can be useful in making decisions for poly-sensitized patients with seasonal AR. To this end, we tried to optimize the prediction of a positive NPT by considering both the VAS outcome (on days of high pollen concentration or summary of the previous season) and the combined serum IgE-specific activity for main grass-pollen molecules Phl p 5 and Cyn d 1 13.

In patients with a VAS score ≥7 for AR severity and IgE-specific activity for both grass molecules (Phl p 5+Cyn d 1) ≥7.25%, a positive outcome for NPT was predicted with a sensitivity of 93% and a specificity of 73% (Fig. 1).

Future possibilities

The correlation between symptom burden and environmental pollen concentrations in patients with seasonal RA is well known 6,43. As is obvious, clinical scores are not allergen-specific and, especially in poly-sensitized patients, may reflect both the immunological “priming” of cross-reactive allergens and the effect of overlapping pollination from various allergenic sources 6. Pollen allergenicity changes with environmental factors such as pollution, humidity, precipitation/storms, and other factors induced by climate change 44. For instance, the rain osmotic impact on the surface of the granules and the cytoplasm releases microparticles that are capable of multiplying the stimulus on sensitive subjects, as happens during periods of asthma exacerbations 44.

Recent studies show that seasonal symptoms, rather than the count of suspected pollen granules, are more related to the aerial concentrations of its most allergenic molecules 45. This suggests that evaluating clinical scales during periods that are “rich” in airborne allergens and measuring the serum IgE-specific activity for these molecules could increase the predictive power for the NPT outcome in pediatric patients. However, this is not the case for all patients with seasonal symptoms, as some have normal serum IgE levels and are classifiable as local AR (so-called “LAR”), thus representing a diagnosis of exclusion.

Acknowledgments

We thank the entire team and all participants of the @IT.2020 pilot study.

Conflicts of interest statement

Tripodi S. is a cofounder of TPS Production.

Funding

The app AllergyMonitor® was kindly provided by TPS Production, Rome, Italy.

Authors’ contribution

BM and TS: prepared the first manuscript draft; all co-authors were actively involved in the discussion and critical review of the manuscript. All authors contributed to the article and approved the submitted version.

History

Received: June 21, 2024

Published: October 7, 2024

Figures and tables

FIGURE 1. “Receiver operating characteristic” (ROC) curves and areas under the curve (AUCs) for allergen sensitization to combined grass molecules and AR visual analog scales (VAS) as predictors of the nasal provocation test (NPT) result. Combined IgE-specific activity to Phl p 5 + Cyn d 1, AUC= 0.82, p < 0.01; VAS for AR severity in the previous pollen season, AUC= 0.77, p < 0.01; Diagnostic algorithm using threshold values for the combined IgE-specific activity to Phl p 5 + Cyn d 1 (≥ 7.25%) and VAS for AR severity in the previous pollen season (≥ 7), AUC = 0.90, p < 0.001 (Modified with permission from [Figure 2]: Barreto M, Tripodi S, Arasi S, Landi M, Montesano M, Pelosi S, Potapova E, Sfika I, Villella V, Travaglini A, Brighetti MA, Matricardi PM, Dramburg S. Factors predicting the outcome of allergen-specific nasal provocation test in children with grass pollen allergic rhinitis. Front Allergy 2023;4:1186353. https://doi.org/10.3389/falgy.2023.1186353).

References

  1. Greiner AN, Hellings PW, Rotiroti G, et al. Allergic rhinitis. Lancet 2011;378:2112–2122. https://doi.org/10.1016/S0140-6736(11)60130-X 3
  2. Wise SK, Lin SY, Toskala E, et al. International consensus statement on allergy and rhinology: allergic rhinitis. Int Forum Allergy Rhinol 2018;8:108-352. https://doi.org/10.1002/alr.22073
  3. Dondi A, Tripodi S, Panetta V, et al. Italian pediatric allergy network (I-PAN). pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity. Pediatr Allergy Immunol 2013;24:742-751. https://doi.org/10.1111/pai.12136
  4. Dramburg S, Grittner U, Potapova E, et al. Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study. Allergy 2024;79:908-923. https://doi.org/10.1111/all.16029
  5. Roberts G, Pfaar O, Akdis CA, et al. EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis. Allergy 2018;73:765-798. https://doi.org/10.1111/all.13317
  6. Pfaar O, Karatzas K, Bastl K, et al. Pollen season is reflected on symptom load for grass and birch pollen-induced allergic rhinitis in different geographic areas-An EAACI Task Force Report. Allergy 2020;75:1099-1106. https://doi.org/10.1111/all.14111
  7. Rodríguez-Domínguez A, Berings M, Rohrbach A, et al. Molecular profiling of allergen-specific antibody responses may enhance success of specific immunotherapy. J Allergy Clin Immunol 2020;146:1097-108. https://doi.org/10.1016/j.jaci.2020.03.029
  8. Augé J, Vent J, Agache I, et al. EAACI position paper on the standardization of nasal allergen challenges. Allergy 2018;73:1597-1608. https://doi.org/10.1111/all.13416
  9. Jang TY, Kim YH. Nasal provocation test is useful for discriminating allergic, nonallergic, and local allergic rhinitis. Am J Rhinol Allergy 2015;29:e100-e104. https://doi.org/10.2500/ajra.2015.29.4214
  10. Hamilton RG, MacGlashan DW, Saini SS. IgE antibody-specific activity in human allergic disease. Immunol Res 2010;47:273-284. https://doi.org/https://doi.org/10. 1007/s12026-009-8160-3
  11. Durham SR, Nelson HS, Nolte H, et al. Magnitude of efficacy measurements in grass allergy immunotherapy trials is highly dependent on pollen exposure. Allergy 2014;69:617-623. https://doi.org/10.1111/all.12373
  12. Senti G, Vavricka BM, Graf N, et al. Evaluation of visual analog scales for the assessment of symptom severity in allergic rhinoconjunctivitis. Ann Allergy Asthma Immunol 2007;98:134-138. https://doi.org/10.1016/S1081-1206(10)60685-0
  13. Barreto M, Tripodi S, Arasi S, et al. Factors predicting the outcome of allergen-specific nasal provocation test in children with grass pollen allergic rhinitis. Front Allergy 2023;4:1186353. https://doi.org/10.3389/falgy.2023.1186353
  14. Bédard A, Basagaña X, Anto JM, et al; MASK study group. Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study. J Allergy Clin Immunol 2019;144:135-143.e6. https://doi.org/10.1016/j.jaci.2019.01.053
  15. Tripodi S, Giannone A, Sfika I, et al. Digital technologies for an improved management of respiratory allergic diseases: 10 years of clinical studies using an online platform for patients and physicians. Ital J Pediatr 2020;46:105. https://doi.org/10.1186/s13052-020-00870-z
  16. Di Fraia M, Tripodi S, Arasi S, et al. Adherence to prescribed E-diary recording by patients with seasonal allergic rhinitis: observational study. J Med Internet Res 2020;22:e16642. https://doi.org/10.2196/ 16642
  17. Costa C, Menesatti P, Brighetti MA, et al. Pilot study on the short-term prediction of symptoms in children with hay fever monitored with e-health technology. Eur Ann Allergy Clin Immunol 2014;46:216-225
  18. Bianchi A, Tsilochristou O, Gabrielli F, et al. The smartphone: a novel diagnostic tool in pollen allergy? J Investig Allergol Clin Immunol 2016;26:204-207. https://doi.org/10.18176/jiaci.0060
  19. Florack J, Brighetti MA, Perna S, et al. Comparison of six disease severity scores for allergic rhinitis against pollen counts a prospective analysis at population and individual level. Pediatr Allergy Immunol 2016;27:382-390. https://doi.org/10.1111/pai.12562
  20. Dramburg S, Perna S, Di Fraia M, et al. Heterogeneous validity of daily data on symptoms of seasonal allergic rhinitis recorded by patients using the e-diary AllergyMonitor®. Clin Transl Allergy 2021;11:e12084. https://doi.org/10.1002/clt2.12084
  21. Klimek L, Bergmann KC, Biedermann T, et al. Visual analogue scales (VAS): Measuring instruments for the documentation of symptoms and therapy monitoring in cases of allergic rhinitis in everyday health care: Position Paper of the German Society of Allergology (AeDA) and the German Society of Allergy and Clinical Immunology (DGAKI), ENT Section, in collaboration with the working group on Clinical Immunology, Allergology and Environmental Medicine of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNOKHC). Allergo J Int 2017;26:16-24. https://doi.org/10.1007/s40629-016-0006-7
  22. Dramburg S, Perna S, Di Fraia M, et al. Prospective (e-diary) vs retrospective (ARIA) measures of severity in allergic rhinoconjunctivitis: an observational compatibility study. Allergy 2023;78:550-553. https://doi.org/10.1111/all.15499
  23. Pfaar O, Bastl K, Berger U, et al. Defining pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis- an EAACI position paper. Allergy 2017;72:713-722. https://doi.org/10.1111/all.13092
  24. ISPRA. POLLnet - Linee guida per il monitoraggio aerobiologico. Available at: https://www.isprambiente.gov.it/files2017/pubblicazioni/manuali-linee-guida/445364_Manuale_linee_guida_151_17.pdf).
  25. Dhami S, Nurmatov U, Arasi S, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis. Allergy 2017;72:1597-1631. https://doi.org/10.1111/all.13201
  26. Nevis IF, Binkley K, Kabali C. Diagnostic accuracy of skin-prick testing for allergic rhinitis: a systematic review and meta-analysis. Allergy Asthma Clin Immunol 2016;12:20. https://doi.org/10.1186/s13223-016-0126-0
  27. Krouse JH, Sadrazodi K, Kerswill K. Sensitivity and specificity of prick and intradermal testing in predicting response to nasal provocation with timothy grass antigen. Otolaryngol Head Neck Surg 2004;131:215-219. https://doi.org/10.1016/j.otohns. 2004.03.024
  28. Pepys J, Roth A, Carroll KB. RAST, skin and nasal tests and the history in grass pollen allergy. Clin Allergy 1975;5:431-442. https://doi.org/10.1111/j.1365-2222.1975. tb01882.x
  29. Petersson G, Dreborg S, Ingestad R. Clinical history, skin prick test and RAST in the diagnosis of birch and timothy pollinosis. Allergy 1986;41:398-407. https://doi.org/10. 1111/j.1398-9995.1986.tb00319.x
  30. Haxel BR, Huppertz T, Boessert P, et al. Correlation of skin test results and specific immunoglobulin E blood levels with nasal provocation testing for house-dust mite allergies. Am J Rhinol Allergy 2016;30:60-64. https://doi.org/10.2500/ ajra.2016.30.4262
  31. Xiao H, Jia Q, Zhang H, et al. The importance of nasal provocation testing in the diagnosis of dermatophagoides pteronyssinus-induced allergic rhinitis. Am J Rhinol Allergy 2022;36:191-197. https://doi.org/10.1177/ 19458924211037913
  32. Zarei M, Remer CF, Kaplan MS, et al. Optimal skin prick wheal size for diagnosis of cat allergy. Ann Allergy Asthma Immunol 2004;92:604-610. https://doi.org/10.1016/S1081-1206(10)61425-1
  33. Al-Ahmad M, Jusufovic E, Arifhodzic N, et al. Sensitization to cat: when is nasal challenge needed? Int Arch Allergy Immunol 2019;179:108-113. https://doi.org/10.1159/000496835
  34. Al-Ahmad M, Jusufovic E, Arifhodzic N. Which skin prick test wheal size detects true allergy to Salsola kali? Eur Ann Allergy Clin Immunol 2021;53:228-233. https://doi.org/10.23822/EurAnnACI.1764-1489.161
  35. Huss-Marp J, Darsow U, Brockow K, et al. Can immunoglobulin E-measurement replace challenge tests in allergic rhinoconjunctivits to grass pollen? Clin Exp Allergy 2011;41:1116-1124. https://doi.org/10. 1111/j.1365-2222.2011.03745.x
  36. Darsow U, Brockow K, Pfab F, et al. Allergens. Heterogeneity of molecular sensitization profiles in grass pollen allergy–implications for immunotherapy? Clin Exp Allergy 2014;44:778-786. https://doi.org/10.1111/cea.12303
  37. Levin M, Rotthus S, Wendel S, et al. Multiple independent IgE epitopes on the highly allergenic grass pollen allergen Phl p 5. Clin Exp Allergy 2014;44:1409-1419. https://doi.org/10.1111/cea.12423
  38. Savi E, Peveri S, Incorvaia C, et al. Association between a low IgE response to Phl p 5 and absence of asthma in patients with grass pollen allergy. Clin Mol Allergy 2013;11:3. https://doi.org/10.1186/ 1476-7961-11-3
  39. Hamilton RG. Provocation tests with objective measures remain more diagnostic than surrogate immunoglobulin E antibody measures of sensitization. Clin Exp Allergy 2011;41:1048-1049. https://doi.org/10.1111/j.1365-2222.2011.03752.x
  40. Gupta RS, Lau CH, Hamilton RG, et al. Predicting outcomes of oral food challenges by using the allergen-specific IgE-total IgE ratio. J Allergy Clin Immunol Pract 2014;2:300-305. https://doi.org/10.1016/j.jaip.2013.12.006
  41. Shamji MH, Kappen JH, Akdis M, et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper. Allergy 2017;72:1156-1173. https://doi.org/10.1111/all.13138
  42. Christensen LH, Holm J, Lund G, et al. Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge. J Allergy Clin Immunol 2008;122:298-304. https://doi.org/10.1016/j.jaci.2008.05.026
  43. Karatzas K, Katsifarakis N, Riga M, et al. New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced rhinitis. Allergy 2018;73:1851-1859. https://doi.org/10.1111/all.13487
  44. D’Amato G, Chong-Neto HJ, Monge Ortega OP, et al. The effects of climate change on respiratory allergy and asthma induced by pollen and mold allergens. Allergy 2020;75:2219-2228. https://doi.org/10.1111/all.14476
  45. Fuertes E, Jarvis D, Lam H, et al. Phl p 5 levels more strongly associated than grass pollen counts with allergic respiratory health. J Allergy Clin Immunol 2024;153:844-851. https://doi.org/10.1016/j.jaci.2023.11.011

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Authors

SIAIP New Digital Technologies Commission - SIAIP

Mario Barreto - NESMOS Department, Faculty of Medicine and Psychology, Pediatric Unit Sant’Andrea Hospital, “Sapienza” University, Rome, Italy

Auro Della Giustina - Private Practice, Parma, Italy

Ifigenia Sfika - Private Practice, Rome, Italy

Stefano Pattini - Pediatric Unit, Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy

Alessandro Travaglini - Department of Biology, Tor Vergata University, Rome, Italy

Maria Antonia Brighetti - Department of Biology, Tor Vergata University, Rome, Italy

Denise De Franco - Department of Biology, Tor Vergata University, Rome, Italy

Alessandro Di Menno Di Bucchianico - Italian National Institute for Environmental Pro- tection and Research (ISPRA), Rome, Italy

Velia Malizia - Institute of Translational Pharmacology, National Research Council (CNR), Palermo, Italy

Salvatore Tripodi - Allergology Service, Policlinico Casilino, Rome, Italy

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How to Cite
Commission, S. N. D. T., Barreto, M., Della Giustina, A. ., Sfika, . I. ., Pattini, . S., Travaglini, A., Brighetti , M. A., De Franco, . D., Di Menno Di Bucchianico , A., Malizia , . V., & Tripodi, S. (2024). Alternatives to the allergen- specific nasal provocation test: role of molecular allergens for grasses in poly-sensitized children with seasonal allergic rhinitis. Italian Journal of Pediatric Allergy and Immunology, 38(3). https://doi.org/10.53151/2531-3916/2024-564
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