Evolution of Quality of Life in Patients with Anaphylaxis Due to LTP Syndrome After 3 Years of Specific Immunotherapy and 1 Year after Treatment Completion
- 1. Reina Sofia University General Hospital, Allergology Section, Spain
- 2. Department of Biochemistry and Molecular Biology B and Immunology of the University of Murcia, Spain
Abstract
Severe food allergies caused by lipid-transporting proteins (LTP) are becoming increasingly prevalent in our environment, predominantly affecting a young population.
CITATION
Carbonell Martínez A, González Pérez A, Escudero Pastor AI, Navarro Garrido C, Miralles López JC, et al. (2023) Evolution of Quality of Life in Patients with Anaphylaxis Due to LTP Syndrome After 3 Years of Specific Immunotherapy and 1 Year after Treatment Completion. JSM Clin Case Rep 11(3): 1221.
INTRODUCTION
The clinical presentation and related symptoms significantly diminish their quality of life. The Food Allergy Quality of Life Questionnaire – Adult form (FAQLQ-AF), developed and validated by Flokstra-de Blok et al. [1], is the first specific questionnaire designed to assess the health-related quality of life (HRQoL) in adult patients allergic to food. This questionnaire has been translated into various languages, including Spanish [2], and cross-validated in the EuropreVall study, a multicenter European food allergy research project with the objective of analyzing the impact of food allergies on the quality of life [3,4].
The LTP syndrome, or Lipid Transfer Protein syndrome, refers to an allergic reaction that can manifest in various ways within the human body. This allergic reaction may initially present as an Oral Allergy Syndrome (OAS) and, in more severe cases, progress to episodes of generalized urticaria affecting the respiratory, digestive, and vascular systems. In extreme situations, this reaction can lead to anaphylaxis, a potentially life-threatening allergic response. Another characteristic of these patients is that they often have rhinitis and/or asthma with pollen allergies.
OBJECTIVES
The primary goal of this study is to investigate the evolution of the quality of life in patients with anaphylaxis due to LTP syndrome after undergoing specific immunotherapy for 3 years and one year after completing the treatment, in comparison to a control group that did not receive immunotherapy.
MATERIAL AND METHODS
Study population: The active group of this study consisted of 21 patients who were over 18 years old and had been diagnosed with anaphylaxis due to LTP syndrome (SLTP). These patients underwent a 3-year treatment regimen involving ALKAbello® peach-specific sublingual immunotherapy (SLIT), which effectively managed their condition. Consequently, they were able to reintroduce a diet that no longer required the exclusion of LTP allergens [5]. On the other hand, the control group included 13 patients with comparable clinical characteristics who made a personal decision not to initiate immunotherapy treatment.
Quality of life test: Patients in the active group underwent a quality of life assessment at the beginning of treatment, at the end of the treatment period, and one year after completing treatment. Patients in the control group underwent the same assessment at the beginning and at the end of the study. The assessment tool used was the S-FAQLQ-AF, which comprises 29 questions grouped into 4 domains for maintaining internal consistency (see Annex 1). Each question is scored from a minimum of 0 to a maximum of 6, resulting in a total score of 174 points (1). The domains or blocks in which the test is structured are: A.- Allergen Avoidance + Dietary Restriction (AADR or Allergen Avoidance and Dietary Restrictions): 11 items: 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 20. B.- Emotional Impact (EI or Emotional Impact): 7 items: 5, 24, 25, 26, 27, 28, 29. C.- Risk of Accidental Exposure (RAE or Risk of Accidental Exposure): 8 items: 7, 13, 14, 15, 16, 17, 18,21. D. Food Allergy Related Health (FAH or Food Allergy Related Health): 3 items: 19, 22, 23.
The domains or blocks in which the test is structured are: (1)
A.- Allergen Avoidance + Dietary Restriction (AADR or Allergen Avoidance and Dietary Restrictions): 11 items: 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 20.
B.- Emotional Impact (EI or Emotional Impact): 7 items: 5, 24, 25, 26, 27, 28, 29.
C.- Risk of Accidental Exposure (RAE or Risk of Accidental Exposure): 8 items: 7, 13, 14, 15, 16, 17, 18, 21.
D.- Food Allergy Related Health (FAH or Food Allergy Related Health): 3 items: 19, 22, 23.
Statistical analysis: Statistical analysis was conducted using R (version 4.0.5). Continuous variables were summarized using measures of central tendency and dispersion, including mean, standard deviation, median, quartiles (25% - Q1 and 75% - Q3), minimum, and maximum values. Normality of continuous variables was assessed using the Shapiro-Wilks test. Independent samples were compared using the independent Student’s T-test for normally distributed data or the Mann-Whitney U test for nonnormally distributed data. For dependent samples, the dependent Student’s T-test was used for normally distributed data, and the Wilcoxon signed-rank test was used for non-normally distributed data. A p-value threshold of <0.05 was considered statistically significant. The ggplot2 package [6] was employed for generating the graphs presented in this study (Tables 1,2) (Graph results 1-5).
Graph 1: Block results A
Graph 2: Block resultsB
Graph 3: Block results C
Graph 4 Block results D
Graph 5: Block results Total.
Table 1: Patient demographics
Patients with treatment | Patients without treatment | |
Total no-missing, n | 21 | 13 |
Missing, n | 0 | 0 |
Gender | ||
Men, n (%) | 7 (33.3%) | 4 (30.8%) |
Women, n (%) | 14 (66.7%) | 9 (69.2%) |
Age | ||
Mean (SD) | 40.1 (11.2) | 40.3 (12.7) |
Median (Q1, Q3) | 42.0 (29.0, 49.0) | 39.0 (30.0, 46.0) |
Min, Max | 22.0, 61.0 | 26.0, 65.0 |
Table 2: Results of each patient's responsesTable-2: M->Men. W->Woman.
Block A | Block B | Block C | Bloc D | Total | |||||||||||||
Age | Sex | Group | A1 | A2 | A3 | B1 | B2 | B3 | C1 | C2 | C3 | D1 | D2 | D3 | T1 | T2 | T3 |
42 | W | Active | 45 | 26 | 37 | 24 | 24 | 25 | 38 | 46 | 36 | 15 | 18 | 13 | 122 | 114 | 111 |
29 | W | Active | 65 | 13 | 10 | 39 | 20 | 10 | 42 | 21 | 9 | 18 | 7 | 2 | 164 | 61 | 31 |
25 | W | Active | 51 | 12 | 28 | 39 | 31 | 29 | 32 | 28 | 33 | 18 | 15 | 15 | 140 | 86 | 105 |
41 | W | Active | 27 | 10 | 8 | 34 | 21 | 13 | 28 | 16 | 9 | 16 | 7 | 4 | 105 | 54 | 34 |
22 | M | Active | 62 | 7 | 20 | 35 | 2 | 31 | 44 | 22 | 13 | 18 | 3 | 12 | 159 | 34 | 76 |
38 | W | Active | 48 | 45 | 5 | 33 | 32 | 6 | 47 | 38 | 8 | 18 | 12 | 6 | 146 | 127 | 25 |
28 | M | Active | 58 | 30 | 27 | 40 | 28 | 25 | 32 | 15 | 30 | 14 | 10 | 7 | 144 | 83 | 89 |
50 | W | Active | 66 | 50 | 7 | 42 | 40 | 22 | 48 | 45 | 22 | 18 | 8 | 6 | 174 | 143 | 57 |
50 | W | Active | 46 | 13 | 0 | 0 | 13 | 12 | 38 | 10 | 8 | 17 | 6 | 11 | 132 | 42 | 31 |
42 | M | Active | 51 | 22 | 4 | 41 | 21 | 12 | 46 | 19 | 8 | 18 | 7 | 4 | 156 | 69 | 28 |
61 | W | Active | 58 | 21 | 21 | 36 | 13 | 13 | 39 | 14 | 12 | 18 | 7 | 1 | 151 | 55 | 47 |
26 | M | Active | 41 | 39 | 12 | 21 | 26 | 6 | 33 | 30 | 17 | 14 | 16 | 6 | 109 | 111 | 41 |
47 | W | Active | 61 | 58 | 26 | 40 | 34 | 24 | 37 | 36 | 24 | 18 | 18 | 10 | 156 | 146 | 83 |
54 | W | Active | 64 | 43 | 46 | 42 | 39 | 38 | 48 | 39 | 42 | 18 | 15 | 15 | 172 | 136 | 141 |
37 | W | Active | 51 | 30 | 5 | 35 | 22 | 10 | 42 | 29 | 15 | 18 | 11 | 3 | 146 | 92 | 33 |
48 | W | Active | 52 | 29 | 37 | 35 | 33 | 34 | 28 | 31 | 29 | 16 | 18 | 16 | 131 | 111 | 116 |
26 | M | Active | 60 | 62 | 24 | 41 | 39 | 13 | 39 | 37 | 18 | 17 | 9 | 3 | 157 | 147 | 58 |
31 | W | Active | 46 | 29 | 7 | 40 | 39 | 33 | 40 | 29 | 19 | 17 | 18 | 14 | 143 | 115 | 73 |
44 | M | Active | 59 | 34 | 16 | 36 | 24 | 12 | 35 | 28 | 12 | 14 | 11 | 3 | 144 | 97 | 43 |
49 | W | Active | 45 | 14 | 15 | 39 | 8 | 19 | 36 | 28 | 28 | 18 | 10 | 14 | 136 | 60 | 76 |
52 | M | Active | 62 | 53 | 25 | 42 | 42 | 17 | 45 | 41 | 19 | 17 | 18 | 11 | 167 | 154 | 72 |
26 | W | Control | 65 | 58 | - | 36 | 36 | - | 42 | 45 | - | 15 | 16 | - | 158 | 155 | - |
27 | W | Control | 45 | 47 | - | 32 | 31 | - | 29 | 31 | - | 16 | 17 | - | 122 | 126 | - |
36 | W | Control | 61 | 61 | - | 41 | 41 | - | 47 | 47 | - | 18 | 18 | - | 167 | 167 | - |
30 | M | Control | 53 | 49 | - | 35 | 23 | - | 39 | 35 | - | 15 | 11 | - | 142 | 118 | - |
65 | W | Control | 52 | 62 | - | 38 | 38 | - | 40 | 44 | - | 13 | 15 | - | 143 | 159 | - |
46 | W | Control | 20 | 15 | - | 20 | 16 | - | 12 | 12 | - | 9 | 9 | - | 61 | 52 | - |
39 | M | Control | 62 | 39 | - | 42 | 37 | - | 44 | 38 | - | 18 | 18 | - | 166 | 132 | - |
42 | W | Control | 10 | 57 | - | 7 | 18 | - | 8 | 35 | - | 3 | 12 | - | 28 | 122 | - |
27 | M | Control | 17 | 37 | - | 18 | 34 | - | 19 | 32 | - | 3 | 14 | - | 57 | 117 | - |
33 | W | Control | 66 | 30 | - | 36 | 37 | - | 43 | 41 | - | 18 | 18 | - | 163 | 126 | - |
43 | W | Control | 36 | 58 | - | 36 | 41 | - | 27 | 47 | - | 12 | 18 | - | 111 | 164 | - |
62 | M | Control | 66 | 23 | - | 42 | 37 | - | 48 | 14 | - | 18 | 8 | - | 174 | 82 | - |
48 | W | Control | 65 | 40 | - | 42 | 37 | - | 43 | 31 | - | 18 | 9 | - | 168 | 117 |
M->Men. W->Woman.
RESULTS
Table 2 displays the individual results of each patient’s responses to the FAQLQ-AF questionnaire, which is divided into domains (A, B, C, D) and provides a total score (T) at three different time points: at the beginning (time 1), after 3 years of treatment (time 2), and 1 year after discontinuing immunotherapy (time 3).
Tables 3 and 4 present the statistical results,
Table 3. Results of the active group at the beginning of treatment, after 3 years of treatment, and 1 year after completing treatment.
Mean (SD) | Median (Q1, Q3) | Min, Max | p. value | |
Block A | ||||
Pre-treatment vs. Post treatment | ||||
Pre-treatment | 53.2 (9.7) | 52.0 (46.0, 61.0) | 27.0, 66.0 | 1.40E-06 |
Post-treatment | 30.5 (16.5) | 29.0 (14.0, 43.0) | 7.0, 62.0 | |
Pre-treatment vs. 1 year post-treatment | ||||
Pre-treatment | 53.2 (9.7) | 52.0 (46.0, 61.0) | 27.0, 66.0 | 9.50E-11 |
1 year post-treatment | 18.1 (12.6) | 16.0 (7.0, 26.0) | 0.0, 46.0 | |
Post-treatment vs. 1 year post-treatment | ||||
Post-treatment | 30.5 (16.5) | 29.0 (14.0, 43.0) | 7.0, 62.0 | 0.006 |
1 year post-treatment | 18.1 (12.6) | 16.0 (7.0, 26.0) | 0.0, 46.0 | |
Block B | ||||
Pre-treatment vs. Post treatment | ||||
Pre-treatment | 35.0 (9.7) | 39.0 (35.0, 40.0) | 0.0 42.0 | 0.003 |
Post-treatment | 26.2 (11.1) | 26.0 (21.0, 34.0) | 2.0, 42.0 | |
Pre-treatment vs. 1 year post-treatment | ||||
Pre-treatment | 35.0 (9.7) | 39.0 (35.0, 40.0) | 0.0 42.0 | 0.0002 |
1 year post-treatment | 19.2 (9.7) | 17.0 (12.0, 25.0) | 6.0, 38.0 | |
Post-treatment vs. 1 year post-treatment | ||||
Post-treatment | 26.2 (11.1) | 26.0 (21.0, 34.0) | 2.0, 42.0 | 0.022 |
1 year post-treatment | 19.2 (9.7) | 17.0 (12.0, 25.0) | 6.0, 38.0 | |
Block C | ||||
Pre-treatment vs. Post treatment | ||||
Pre-treatment | 38.9 (6.2) | 39.0 (35.0, 44.0) | 28.0, 48.0 | 0.00014 |
Post-treatment | 28.7 (10.4) | 29.0 (21.0, 37.0) | 10.0, 46.0 | |
Pre-treatment vs. 1 year post-treatment | ||||
Pre-treatment | 38.9 (6.2) | 39.0 (35.0, 44.0) | 28.0, 48.0 | 8.20E-07 |
1 year post-treatment | 19.6 (10.2) | 18.0 (12.0, 28.0) | 8.0, 42.0 | |
Post-treatment vs. 1 year post-treatment | ||||
Post-treatment | 28.7 (10.4) | 29.0 (21.0, 37.0) | 10.0, 46.0 | 7.00E-04 |
1 year post-treatment | 19.6 (10.2) | 18.0 (12.0, 28.0) | 8.0, 42.0 | |
Block D | ||||
Pre-treatment vs. Post treatment | ||||
Pre-treatment | 16.9 (1.5) | 18.0 (16.0, 18.0) | 14.0, 18.0 | 0.001 |
Post-treatment | 11.6 (4.8) | 11.0 (7.0, 16.0) | 3.0, 18.0 | |
Pre-treatment vs. 1 year post-treatment | ||||
Pre-treatment | 16.9 (1.5) | 18.0 (16.0, 18.0) | 14.0, 18.0 | 9.40E-05 |
1 year post-treatment | 8.4 (5.0) | 7.0 (4.0, 13.0) | 1.0, 16.0 | |
Post-treatment vs. 1 year post-treatment | ||||
Post-treatment | 11.6 (4.8) | 11.0 (7.0, 16.0) | 3.0, 18.0 | 0.014 |
1 year post-treatment | 8.4 (5.0) | 7.0 (4.0, 13.0) | 1.0, 16.0 | |
Total score | ||||
Pre-treatment vs. Post treatment | ||||
Pre-treatment | 145.4 (18.6) | 146.0 (136.0, 157.0) | 105.0, 174.0 | 5.50E-06 |
Post-treatment | 97.0 (37.5) | 97.0 (61.0, 127.0) | 34.0, 154.0 | |
Pre-treatment vs. 1 year post-treatment | ||||
Pre-treatment | 145.4 (18.6) | 146.0 (136.0, 157.0) | 105.0, 174.0 | 2.40E-09 |
1 year post-treatment | 65.2 (33.2) | 58.0 (34.0, 83.0) | 25.0, 141.0 | |
Post-treatment vs. 1 year post-treatment | ||||
Post-treatment | 97.0 (37.5) | 97.0 (61.0, 127.0) | 34.0, 154.0 | 0.002 |
1 year post-treatment | 65.2 (33.2) | 58.0 (34.0, 83.0) | 25.0, 141.0 |
Table 4: Comparison of results between the active group and the control group.
Box plots and whiskers (1, 2, 3, 4, 5) (boxplot) have been used to represent the results.
Mean (SD) | Median (Q1, Q3) | Min, Max | p. value | |
Block A | ||||
Patient with treatment | -22.8 (15.4) | -21.0 (-31.0, -16.0) | -55.0, 2.0 | 0.021 |
Patient without treatment | -3.2 (24.9) | -4.0 (-23.0, 10.0) | -43.0, 47.0 | |
BlockB | ||||
Patient with treatment | -8.7 (11.6) | -6.0 (-13.0, -1.0) | -33.0, 13.0 | 0.011 |
Patient without treatment | 0.1 (7.3) | 0.0 (-5.0, 1.0) | -12.0, 16.0 | |
BlockC | ||||
Patient with treatment | -10.2 (10.0) | -9.0 (-17.0, -3.0) | -28.0, 8.0 | 0.029 |
Patient without treatment | 0.8 (14.9) | 0.0 (-4.0, 4.0) | -34.0, 27.0 | |
BlockD | ||||
Patient with treatment | -5.3 (5.4) | -6.0 (-10.0, 0.0) | -15.0, 3.0 | 0.009 |
Patient without treatment | 0.5 (6.0) | 0.0 (0.0, 2.0) | -10.0, 11.0 | |
Total score | ||||
Patient with treatment | -48.4 (36.2) | -47.0 (-76.0, -19.0) | -125.0, 2.0 | 0.008 |
Patient without treatment | -1.8 (49.8) | -3.0 (-34.0, 16.0) | -92.0, 94.0 |
comparing the scores of the different domains and the total score of the questionnaire at the three time points within the active group. Additionally, these tables compare the results of the active group with those of the control group. The findings reveal statistically significant differences in all domains and the total score of the questionnaire. Moreover, statistically significant distinctions are evident when comparing the results with the control group.
DISCUSSION
Health-related quality of life (HRQoL) is a term that encompasses various aspects of a person’s well-being, including the impact of disease and its treatment on disability, daily functioning, and overall quality of life. It also reflects how perceived health affects a person’s ability to lead a fulfilling life. Specifically, HRQoL measures the value a person places on their life span, considering impairments, functional states, perceptions, and opportunities influenced by factors such as disease, injury, treatment, and policy [7].
Two primary types of tools are used to assess the impact of different diseases on patients’ quality of life: generic and diseasespecific questionnaires. Generic questionnaires allow researchers to compare various clinical conditions, while disease-specific questionnaires focus on problems associated with a particular disease. Disease-specific questionnaires are better equipped to detect small changes in HRQoL following treatment [8].
According to the 2005 National Allergological Survey of Spain, patients with food allergies, assessed using the SF-12 Generic Questionnaire (physical and mental scales), perceived their quality of life as worse than that of 75% of the Spanish population of similar age and sex [9].
Currently, there is a growing body of research on the quality of life of patients with food allergies [8-10]. Additionally, numerous trials on sublingual immunotherapy (SLIT) in food allergies explore different approaches to managing this clinical condition, including peanut and peach immunotherapy. However, most studies do not specifically examine changes in quality of life after peach or peanut immunotherapy [11,12]. Therefore, it is essential to recognize that lipid-transfer protein syndrome (LTLS) can be severe in many cases and profoundly affect patients’ HRQoL. Thus, it becomes crucial to assess not only the safety and efficacy of SLIT-peach® immunotherapy but also the improvements in HRQoL following long-term SLIT administration and the sustainability of these positive effects after treatment cessation. The significant enhancement in the quality of life observed in our patients following a 3-year course of SLIT-peach® suggests further evidence of the treatment’s beneficial effects.
With this study, our aim was to track the evolution of the questionnaire over the four-year follow-up period of our patients. We have confirmed that the S-FAQLQ-AF (2) is a valuable and indispensable tool for monitoring this patient population.
We believe that this study is groundbreaking in terms of collecting a significant number of patients with LTP syndrome and conducting a four-year follow-up. Based on our findings, we can conclude that patients with anaphylaxis due to LTP syndrome, who underwent treatment with SLIT-peach®, experienced a substantial improvement in their quality of life from the beginning of treatment to its completion (3 years). Furthermore, this enhanced quality of life continued to improve globally up to one year after discontinuing immunotherapy.
CONCLUSIONS
Treatment with SLIT-peach® improves the quality of life of patients, and this improvement is sustained after its completion. This is currently the first 4-year follow-up on anaphylactic diseases in patients with LTP syndrome.
REFERENCES
5. Alejandra González, Antonio Carbonell Martínez, Ana Isabel Escudero Pastor, Cristina Navarro Garrido, and Juan Carlos MirallesLópez. Pru p 3 oral immunotherapy efficacy, induced immunological changes and quality of life improvement in patients with LTP syndrome. Clin Transl Allergy. 2020; 10: 2045-7022.
6. Wickham, Hadley. Ggplot2: elegant graphics for data analysis. New York: Springer. 2009;1(6):1-7.