Respiratory allergy in Mexican patients with cystic fibrosis
C. Torres-Lozano*, Mª. E. Núñez-Núñez*, A. Pedroza-Meléndez*, J. L. Lezana F.** and J. G. Huerta-López*
*Department of Allergy and Clinical Immunology. National Institute of Pediatrics. Mexico, City. **Mexican Association of Cystic Fibrosis. Mexico, City.
Correspondence:
Carlos Torres-Lozano, MD, M. en Cs.
Level D, Centre Block
Southamptom General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
E-mail: ctl1@soton.ac.uk
SUMMARY
Backgrounds: the purpose of this study was to investigate the presence of respiratory allergy in 30 Mexican patients bearing cystic fibrosis (CF).
Methods and results: all patients completed a clinical history, had a physical examination, total serum IgE, nasal and blood eosinophils determinations and evaluation of skin prick tests for 36 allergens.
In 26.6% of the patients included in the study was detected respiratory allergy diagnosed on clinical and laboratory analyses. Skin prick tests of 11 (36.6%) of the patients were positive to at least one allergen and Aspergillus fumigatus (A. fumigatus) was the most frequently observed allergen in 23% of the cases.
Conclusions: we have demostrated in this study that Mexican patients also present a coexistence of respiratory allergy in patients bearing CF.
Key words: Cystic fibrosis. Respiratory allergy. Allergens.
INTRODUCTION
Cystic fibrosis (CF) is a multisystem disease occurring in about 1:1600 living new born in the caucasian population and is inherited as a recessive autosomal feature in which the genetic abnormality is located in chromosome 7 (1). It is well known that a large number of patients with CF, even without the diagnosis, seek medical consultation for symptoms that suggest an allergic type disorder (2).
In 1949, Lowe and colleagues established that 30% of the relatives of the CF patients had a clinical history of allergic disease (3). Others studies, report a prevalence of allergy in patients with CF of 16 and 24% of the cases respectively (2, 4). Furthermore, a high positive skin reaction to A. fumigatus has been detected (5, 6).
The purpose of this study was to search the presence of respiratory allergy in CF on Mexican patients.
METHODS
The present study included 30 patients of both sexes suffering CF. The diagnosis of CF was achieved by expert medical doctors from the Mexican Association of Cystic Fibrosis by a characteristic clinical course and a positive sweat test. All subjects involved in this clinical research study attended an annual medical check up at this national center for deteccion of CF and all of them were considered to bear a mild disease according with Shwachman-Kulczicki clinical score (7).
After clinical history, where hypersensitivity for allergens as well as family atopic backgrounds were sought, all patients had skin prick tests to 36 allergens (pollens, house dust mites, fungus including A. fumigatus, food, animal danders), by using glycerinated antigens (Holliestier-Stier). Histamine was used as positive control and glycerol as negative control. The evaluation of the skin reactions was performed 15 minutes after the puncture, and any response (wheal) equal or superior to 50% of the wheal produced by the histamine, was considered positive (8).
In all patients included, we determine the concentration of total serum IgE with the immunoenzymatic test (Enzignost IgE monoclonal from Behring Laboratories). Nasal and blood eosinophils were stained by the Wright technique and considered positive when 10% or more per field and 500 or more esosinophils/mm3 were observed respectively. The final diagnosis of respiratory allergy and the analysis of the results on this patients was established by clinical fellows in allergology from de National Institute of Pediatrics.
Student''s t or Mann-Whitney U for the interval scales and Chi squared test for nominal scales were used to establish the difference between the two groups (patients CF-allergic vs CF-nonallergic).
RESULTS
Sixteen patients were female (age range 1 to 31 years old; mean age 11.1) and 14 were male (age range lto 40 years old; mean age 8.6).
Eight (26.6%) patients with CF were detected to bear respiratory allergy disease, diagnosed after analysis of clinical history, physical examinations and evaluation of skin prick tests, quantification of nasal and blood eosinophils and total serum IgE. Six had bronchial asthma, 1 allergic rhinitis and one had the association of both and they were considered as CF-allergic patients (table I). CF-allergic patients had IgE levels, nasal and blood eosinophils count greater than CF-nonallergic patients and this was statistically significant as shown in table II. Finally, eleven (36.6%) patients had at least one positive skin prick test and A. fumigatus was the most common allergen in 7 (23%) of the cases.
| Table I Patients with the association of respiratory allergy and cystic fibrosis | ||||||
| Case No. | Age years | Sex | Pathology | Skin sensitivity | Nasal eosinophils | Blood eosinophils count |
| 1 | 4 | M | AR | Dpt, Af | + | 475 |
| 2 | 20 | M | A | Dpt, Frax, Af | + | 650 |
| 3 | 5 | M | A | Df, PA, Frax, CHe | + | 500 |
| 4 | 21 | M | AR-A | Af, Df | + | 564 |
| 5 | 20 | F | A | Df | | 819 |
| 6 | 5 | F | A | Af, Dpt, SM | + | 100 |
| 7 | 1 | M | A | Dpt, P | + | 196 |
| 8 | 4 | F | A | Dpt | | 570 |
| A: Asthma; AR: Allergic rhinitis; Af: Aspergillus fumigatus; Che: Chenopodium; Df: Dermatophagoides farinae; Dpt: Dermatophagoides pteronyssinus; Frax: Fraxinus; P: Peach; PA: Populus alba; SM: Shinus molle. | ||||||
| Table IIComparison between allergic and nonallergic cystic fibrosis patients | |||
| Group | Allergic (8) | Nonallergic (22) | p Value |
| Nasal | |||
| Eosinophills % | 88 | 32 | < 0.05 |
| Count of blood | |||
| eosinophils | 484 ± 234 | 112 ± 152 | < 0.001 |
| (mean ± SD*) | |||
| IgE (Ul/ml) | |||
| (mean ± SD*) | 553 ± 873 | 37 ± 79 | < 0.001 |
DISCUSSION
The coexistence of respiratory allergy under the form of bronchial asthma and allergic rhinitis or both pathologies in patients with CF is well known in anglosaxon population (4, 9). In the present work, we were able to demonstrate that Mexican patients present such coexistence as well. In several studies, the incidence of respiratory allergy reported in patients with CF have ranged from 16% to 38% (2, 4, 9) and we found an incidence of 26.6% in this study.
Although the cause or mechanisms of high atopic prevalence in this illness remains still unknown, the phenomenon might be acquired as a result of a high antigenic access through the tracheobronchial tree produced by an increase in the permeability of the bronchial mucosa (10), by a defective secretory IgA system (11), by trapping antigens in infected areas of the lungs, in fact, the highest IgE levels has been associated with chronic Pseudomonas colonization and frequent exacerbation of infection (12) or through insufficiency in the antigen clarification due to ciliotoxic factors (13), which alltogether would get constant stimulation of the immune system for the production of IgE. Furthermore, another suggestion is that the high prevalence of atopy is a function of the genetic defect in CF (14).
Positive skin prick test to at least one allergen was found in this study in 36.6% of the cases, in contrast with other reports, with percentages ranging from 45 to 88% (5, 9, 13, 15, 16). The most frequent allergen was A. fumigatus positive in 23% of the total cases in comparison with other studies with percentages between 27.7% to 58.6% (5, 6, 9, 15).
That this skin sensitivity occurs predominatly to moulds spores is of particular interest. Under normal circunstances, despite high concentrations of exposure, no sensitization will occur (17). However, it has been known that exposure to high concentrations of hyphal elements rather than spores will have a chance of producing sensitivity. Thus, in the CF patients with progressively more severe airway inflammation, spores will become trapped and will not be cleared rapidly. There will then be sufficient time for hyphal growth to occur with consequent release of allergenic proteins and sensitization will then take place (18, 19). Furthermore, it is very well known that allergic bronchopulmonary aspergillosis (ABPA) does occur in up to 10% of patients with CF, and is very clearly associated with a more rapid decline in lung function and sometimes this leads to the development of proximal bronchiectasis (20).
Although there are many controversies regarding the role that atopy plays in CF, a greater knowledge of the initiation of the hypersensitivity phenomenon and the regulation of the vicious circle in the immunoinflammatory response in this disease might indicate future ways of lung protection and prolonging the survival of these patients.
RESUMEN
Antecedentes: el propósito de este estudio fue investigar la presencia de alergia respiratoria en 30 pacientes mexicanos con fibrosis quística (FQ).
Método y resultados: en todos los pacientes se completó la anamnesis, y todos fueron sometidos a exploración física, determinación de IgE sérica total, y eosinófilos nasales y sanguíneos, y pruebas cutáneas para 36 alergenos.
En el 26,6% de los pacientes que fueron incluidos en el estudio se detectó alergia respiratoria diagnosticada mediante exploración clínica y analítica. Las pruebas cutáneas de 11 (36,6%) de los pacientes fueron positivas al menos a un alergeno y Aspergillus fumigatus (A. fumigatus) fue el alergeno observado con más frecuencia, en el 23% de los casos.
Conclusiones: hemos demostrado en este estudio que en los pacientes mexicanos coexiste también la alergía respiratoria en los pacientes con FQ.
Palabras clave: Fibrosis quística. Alergia respiratoria. Alergenos.
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