Cockroach ( Blattella Germanica ) Sensitization is Associated with Coexistence of Asthma and Allergic Rhinitis in Childhood

Abstract

Cockroaches are regarded as important environmental allergens associated with respiratory diseases. The aim of our study was to determine cockroach sensitization patterns in a large number of children, and to document its association with other allergens along with the presence and severity of allergic diseases. Children with various symptoms of suspected atopic diseases such as asthma, allergic rhinitis/conjunctivitis, and atopic dermatitis, with at least 1 positive skin test to a panel of 15 inhalant allergens were included in the study. Blood eosinophil counts and serum total IgE levels were measured, and total atopy index was calculated. A total of 1,513 children were analyzed, and 385 (25.4%) found to have cockroach sensitization. At univariate analyses, asthma, allergic rhinitis, and coexistence of asthma and allergic rhinitis were more frequent in children with cockroach sensitization compared with those without cockroach sensitization (P < 0.05). There was also a novel association between sensitizations of cockroach and pine, aspergillus allergens. However, multivariate analyses revealed a positive association between cockroach sensitization and age at diagnosis, coexistence of asthma and allergic rhinitis, and sensitizations of certain allergens; that is, house dust mite, aspergillus, and pine whereas a negative association for sensitizations of mold mix and weed mix. In a pediatric population with atopic diseases, cockroach sensitization appears to be detected in elder children with coexisting asthma and allergic rhinitis. Presence of house dust mite, pine, and aspergillus sensitizations predict cosensitization of cockroach whereas weed and mold mix sensitizations decrease the possibility of detecting a sensitization.

Introduction

Environmental allergens are considered an important factor in the development of respiratory allergic diseases. Cockroaches, which are generally seen in both indoor and outdoor environments, are usually linked with allergic reactions in humans. In cockroach allergy, tropomyosin causes a cross reaction with house dust mite, parasites, and shrimp allergens, and it is responsible for allergic reactions in sensitive patients.^1,2

According to the National Cooperative Inner City Asthma Study, a combination of sensitization and exposure to cockroach allergens is a risk factor for the severity of asthma in children in the United States.³ Additionally, a number of studies have demonstrated that up to 36%–47% of atopic patients with asthma in the United States are sensitized to cockroach allergens, and those with cockroach sensitivity have more severe disease.^3,4 On the other hand, European studies on children and adults show a high variability in cockroach sensitization with a percentage varying from 0.5% to 25.7%,^5–7 which appears quite a bit lower than the U.S. data. In Turkey, cockroaches are important indoor allergens, and a rate of cockroach sensitization of 20% in adults, and 14.8%–25.7% in the pediatric age has previously been reported. However, these studies are usually based on a limited number of cases with a relatively small number of allergens in the skin test panels.^8–10

The aim of our study was to determine cockroach (Blattella germanica) sensitization in a large number of children in a cross-sectional survey, and to document its association with other allergens along with the presence and severity of allergic diseases such as asthma, allergic rhinitis/conjunctivitis, and atopic dermatitis.

Materials and Methods

Patients

Children who were referred to the pediatric allergy outpatient clinic of the Antalya Education and Research Hospital from April 2011 to May 2014 with various symptoms of suspected atopic diseases such as asthma, rhinitis/conjunctivitis, and atopic dermatitis, with at least 1 positive skin test to a panel of 15 inhalant allergens were included in the study. To prevent inter-observer variability, the same physician (F.C) made all of the diagnoses, and performed and evaluated all tests.

All children and their parents were interviewed and a questionnaire was filled out. The questionnaire consisted of several questions, including age, gender, clinical history, age at onset of atopic disease, history of previous hospital admissions for asthma, family history for asthma/rhinitis, presence of mold/dampness at home, presence of carpet in the child's bedroom, maternal smoking in pregnancy, presence postnatal of 1 or more smokers at home, presence of pets at home, and day care attendance <3 years. The study was approved by the Local Ethics Committee of the Antalya Education and Research Hospital.

Skin tests

Skin prick test (SPT) was performed in all participants with an optimal panel of 15 aeroallergens previously identified as common in Turkey,¹¹ including house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cockroach (Blattella germanica), mold mix (Alternaria tenuis, Botrytis cinerea, Cladosporium herbarum, Curvularia lunata, Fusarium moniliforme, and Helmintthosporium halodes) aspergillus (Aspergillus fumigatus), and cat, dog, grass mix (Holcus lanatus, Dactylis glomerata, Lolium perene, Phleum pretense, Poa pratensis, and Festuca pratensis), weed mix (Artemisia vulgaris, Urtica dioica, Taraxacum vulgare, and Plantago lanceolata), cereal mix (Hordeum vulgare, Avena sativa, Secale cereale, and Triticum sativum), tree mix (Alnus glutinosa, Corylus avellana, Populus alba, Ulmus scarab, and Salix caprea). About 10 mg/mL of histamine phosphate and 0.9% sterile saline were applied as positive and negative controls, respectively. This panel had been modified and enriched by adding several allergens, including feather mix, paroquet, and particularly pine and olive, which are frequent allergens unique to the study center. Commercially available extracts (Allergopharma, Hamburg, Germany) were used, and tests were performed according to international standard procedures. Use of antihistamines was discontinued for 2 weeks before the SPT. A positive test was defined as a mean wheal size of >3 mm after subtraction of the negative control. Sensitization was defined as having at least 1 positive skin test response to 1 of the aeroallergens tested. The total atopy index was defined as the total number of allergens out of 15 tested to which each subject had a positive response for allergens.⁶

Blood eosinophil counts and serum total IgE levels

Blood eosinophil counts were determined by Coulter Counter (Beckman Coulter, Fullerton, CA). Serum total IgE levels were measured with the ImmunoCAP system (Phadia AB, Uppsala, Sweden) according to the manufacturer's instructions.

Diagnosis and classification of asthma

In children with symptoms of asthma, the diagnosis was made in the presence of reversible airway obstruction as defined by at least a 12% improvement in FEV1 following bronchodilator administration, or improvement in asthma symptoms after oral/inhaled steroid therapy. In younger children who could not cooperate with spirometry, asthma was diagnosed by a history of recurrent episodes of wheezing, cough, and a favorable therapeutic response to asthma treatment. The severity of asthma was graded according to the Global Initiative for Asthma guidelines.¹²

Diagnosis of allergic rhinitis/conjunctivitis

Allergic rhinitis was defined by the occurrence of symptoms such as rhinorrhea, nasal obstruction, nasal itching, and sneezing upon exposure to sensitized allergen for at least a minimum duration of 2 years.¹³ Allergic conjunctivitis was defined as itching flush, lacrimation, eyelid swelling, and watery eyes.¹⁴

Diagnosis of atopic dermatitis

Atopic dermatitis was defined by the presence of pruritus and relapsing eczematous rashes typically found over flexor surfaces.¹⁵

Statistical analysis

SPSS Statistics Version 21.0 (IBM, Chicago, IL) was used for all calculations. Descriptive data for categorical variables were expressed as frequencies. The distributions of all numerical variables including current age, age at diagnosis, total IgE levels, and blood eosinophil counts were skewed, thus results were summarized as medians and interquartile ranges. Group comparisons were established using Mann–Whitney tests for medians (and ranges), and the chi-square test for categorical variables. The association between demographic parameters and cockroach sensitization (and other sensitizations) was analyzed using logistic regression modeling. Variables with a P < 0.20 in univariable analysis were used for multivariable analysis. For the multivariable analysis, variables with a P < 0.20 in univariable analysis were further entered into logistic regression analysis to determine independent factors associated with cockroach sensitization. The strength of association between cockroach sensitization and risk factors was measured using odds ratios (ORs) and 95% confidence intervals (CIs). A P < 0.05 was considered statistically significant.

Results

A total of 1,513 children (868 male, 57.4%) with a median age of 10.0 (7.5–13.5) years were included in the study. Within the study group, 385 subjects (25.4%) had cockroach sensitization. There was no association between gender and cockroach sensitization within the study group. The median age of children with cockroach sensitization was higher than those without cockroach sensitization [median, interquartile range; 10.6 (7.8–14.3) year versus 9.7 (7.4–13.2) years, respectively, P = 0.028]. Additionally, the median age of diagnosis of children with cockroach sensitization was also higher than those without cockroach sensitization [9.1 (6.2–12.3) years versus 8.0 (5.8–11.6) years, respectively, P = 0.009].

When the association between cockroach sensitization and the presence of asthma and other allergic diseases was evaluated, it was found that asthma, allergic rhinitis, and coexistence of “asthma and allergic rhinitis” were more frequent in children with cockroach sensitization compared with those without cockroach sensitization, P < 0.05. However, no relationship was found between severe asthma and cockroach sensitization (Table 1).

Table 1.

Demographic Features of the Study Group Along with Cockroach Sensitization

	Study group n:1513	CR (+) n:385	CR (−) n:1128	P^a
Current age, years	10.0 (7.5–13.5)	10.6 (7.8–14.3)	9.7 (7.4–13.2)	0.028
Age at the diagnosis, years	8.3 (5.9–11.8)	9.1 (6.2–12.3)	8.0 (5.8–11.6)	0.009
Male sex (%)	57.4	57.4	57.4	0.99
Asthma (%)	66.6	73.2	64.4	0.001
Severe asthma (%)	5.3	5.7	5.1	0.71
Allergic rhinitis (%)	64.4	71.2	62.1	0.001
Asthma and allergic rhinitis (%)	35.2	46.5	31.4	<0.001
Allergic conjunctivitis (%)	4.3	3.9	4.4	0.65
Atopic dermatitis (%)	5.4	3.6	6.0	0.07
Smoking in pregnancy (%)	5.4	6.5	5.0	0.25
Prematurity (%)	3.6	3.6	3.5	0.93
History of RDS (%)	3.0	3.4	2.8	0.59
History of recurrent wheezing <3 years (%)	52.1	58.4	50.0	0.004
Family history of allergic disease (%)	53.7	56.6	52.7	0.18
Mold/dampness at home (%)	17.3	20.3	16.2	0.07
Carpet in child's bedroom (%)	81.4	82.3	81.0	0.57
Pets presence at home (%)	18.0	20.0	17.3	0.23
One or more smokers at home (%)	37.5	36.4	37.9	0.58
Day care attendance <3 years (%)	4.8	4.2	5.0	0.52
Household member with Tb (%)	4.3	4.4	4.3	0.89
Atopy index	3.0 (2.0–5.0)	4.0 (2.0–6.0)	3.0 (1.0–5.0)	<0.001
Total IgE (kU/L)	186 (69–458)	279 (120–619)	154 (56–405)	<0.001
Eosinophil count/mm³	300 (200–600)	400 (200–700)	300 (200–500)	<0.001

P value that belongs to statistical difference between CR (+) and CR (−) groups.

Data in parenthesis represent the median and interquartile ranges (25–75th percentiles).

Bold indicates statistically significant values.

CR, cockroach; RDS, Respiratory distress syndrome; Tb, tuberculosis.

When the association of cockroach sensitization was evaluated with the presence of other risk factors, such as smoking in pregnancy, prematurity, history of respiratory distress syndrome, family history of allergic disease, presence of mold/dampness at home, carpet in the child's bedroom, presence of pets (cat/dog/paroquet) at home, 1 or more smokers at home, day care attendance <3 years, and household member with tuberculosis, no statistically significant difference was found except for the history of recurrent wheezing <3 years (Table 1). Additionally, the atopy index, serum total IgE and eosinophil count were significantly higher in patients with cockroach sensitization compared with children without cockroach sensitization, P < 0.05. The monosensitization rate (sensitization only with cockroach) was 3.1% in the study group.

As we compared the accompanying aeroallergen sensitization patterns of the study group, we found that accompanying house dust mite, pine, aspergillus and dog sensitizations were significantly more frequent in children with cockroach sensitization, whereas grass mix, olive, tree mix, and weed mix sensitizations were more frequent in children without cockroach sensitization (Table 2).

Table 2.

Sensitization Patterns According to Cockroach Sensitivity

Allergens	Overall (%)	CR (+) (%)	CR (−) (%)	P
House dust mite	61.6	84.2	53.9	<0.001
Grass mix	40.1	32.7	42.6	0.001
Cereal mix	40.0	39.5	40.2	0.81
Olive	32.3	27.0	34.1	0.01
Pine	28.5	35.8	26.0	<0.001
Tree mix	25.8	19.7	27.9	0.002
Weed mix	23.5	16.4	25.9	<0.001
Mold mix	23.2	19.7	24.4	0.063
Animal mix	14.3	13.8	14.5	0.71
Aspergillus	12.9	24.4	9.0	<0.001
Cat dander	13.2	13.0	13.3	0.88
Dog dander	12.7	15.8	11.6	0.03
Paroquet	10.6	11.2	10.5	0.70

Bold indicates statistically significant values.

Multivariable associations between sensitization to cockroach and other risk factors including demographic features and accompanying aeroallergens are shown in Table 3. Briefly, we found positive associations between cockroach sensitization and age at diagnosis, coexistence of “asthma and allergic rhinitis,” accompanying house dust mite, pine, and aspergillus sensitizations, whereas there were negative relationships with accompanying weed mix and mold mix sensitizations.

Table 3.

Multivariable Logistic Regression Analysis for Cockroach Sensitization

	OR	95% CI	P
Age at diagnosis	1.06	1.03–1.1	0.001
Asthma and allergic rhinitis	1.75	1.35–2.27	<0.001
House dust mite	3.58	2.62–4.89	<0.001
Grass mix	1.04	0.72–1.49	0.84
Olive mix	0.79	0.57–1.11	0.18
Pine	1.87	1.40–2.52	<0.001
Tree mix	0.72	0.50–1.02	0.067
Weed mix	0.49	0.34–0.73	<0.001
Mold mix	0.57	0.41–0.81	0.001
Aspergillus	2.97	2.05–4.31	<0.001
Dog dander	1.42	0.98–2.10	0.068

Data are expressed as OR and 95% CI.

Bold indicates statistically significant values.

OR, odds ratio; CI, confidence interval.

Additionally, we evaluated the association of co-occurrence of “asthma and allergic rhinitis” in 4 different sensitization states (Table 4). Shortly, we found statistically significant association only in the house dust mite-positive group. There was no association with co-occurrence of “asthma and allergic rhinitis” and sensitization to other allergens (animal mix, cat, and dog).

Table 4.

Different Sensitization States to “Asthma and Allergic Rhinitis”

	Asthma and allergic rhinitis (%)	P
House dust mite (+) n:932	39.8	<0.001
House dust mite (−) n:581	27.9
Animal mix (+) n:217	38.7	0.25
Animal mix (−) n:1296	34.6
Cat (+) n:200	40.0	0.13
Cat (−) n:1313	34.5
Dog (+) n:192	37.5	0.48
Dog (−) n:1321	34.9

Bold indicates statistically significant values.

Furthermore, we evaluated the prevalence of multiple indoor and outdoor allergen sensitization in patients with “asthma and allergic rhinitis.” Shortly, “asthma and allergic rhinitis” was seen more frequently in multiple indoor allergen sensitization (P < 0, 01). However,”asthma and allergic rhinitis” was not associated with multiple outdoor allergen sensitization.

Discussion

In this cross-sectional study, we found that cockroach sensitization is associated with the coexistence of “asthma and allergic rhinitis” and older age in children. We also determined that there was a positive relationship between CR sensitization and, house dust mite, pine pollen, and aspergillus sensitizations along with a negative relationship with weed pollen and mold sensitizations.

Cockroaches are a source of indoor allergens, which can cause allergic diseases such as “asthma and allergic rhinitis.” Cockroach sensitivity in children and adults has different prevalence rates among countries, strongly depending on climate and humidity. In Turkey, a rate of cockroach sensitization of 20% in adults, and of 14.8%–25.7% in the pediatric age has previously been reported from the Ankara province.^8,10,16 Because Blattella Germanica is the most commonly encountered cockroach species in Turkey, we studied Blattella Germanica subspecies, and found a prevalence of 25.4%, which is similar to previous Turkish studies.^8–10 Cockroach sensitivity was detected at a very high rate (73.2%) in patients with asthma. Additionally, the monosensitization rate for cockroach sensitization was found to be 3.1%. Mungan et al. reported that the frequency of cockroach sensitization was 25.7% and the monosensitization rate was 2.4%.⁸ Yilmaz et al. reported that the frequency of cockroach sensitization was 19% and the monosensitization rate was 1%.¹⁰ Lastly, Grutta et al. have reported that the frequency of cockroach sensitization was 10.5% and the monosensitization rate was 1.3% in southern Italy, which has similar climatic conditions as Antalya.⁶

In several studies, it has been indicated that cockroach sensitization is an important risk factor for asthma severity,^17,18 but in our study group no relationship was found between severe asthma and cockroach sensitivity. However, we have found that cockroach sensitization was related to the coexistence of “asthma and allergic rhinitis” in atopic children.

When we compare cockroach sensitization with the presence of other risk factors, we found that only a history of recurrent wheezing <3 years showed a statistically significant relationship. This finding supports the results of a recent study that emphasizes allergen exposure over the first 3 years being associated with allergic sensitization, and sensitization at age 3 years being related to recurrent wheeze.¹⁹

Additionally, in our study group the atopy index, serum total IgE levels, and blood eosinophil counts were significantly higher in patients with cockroach sensitization than those without cockroach sensitization. These data are compatible with the literature; however, in previous studies eosinophil count was not associated with cockroach sensitization.⁶ In a study by Sohn et al. it was reported that German cockroach extract induces activation of human eosinophils to release cytotoxic inflammatory mediators.²⁰ Single case reports have also shown high IgE levels and hyper-eosinophilia in cockroach sensitivity.²¹ Moreover, in our study group, the detection of a significantly higher atopy index only in cockroach-positive patients might suggest that cockroach sensitization can play an important role as a relevant allergen exposure to achieve multiple sensitizations. As a result, cockroach sensitization should always be kept in mind in cases with high IgE levels, eosinophilia and multiple sensitizations.

In this study, house dust mite allergy was the most frequently seen allergen sensitivity in the study population with a rate of 61.6%. A significant association was found between house dust mites and cockroach sensitization. Most of the children (84.2%) sensitized to house dust mites were also sensitized to cockroach. In multivariable logistic regression analysis, patients with house dust mite sensitization have a 3.58 times higher risk to have cockroach sensitization. This high ratio can be explained by the antigenic similarity between house dust mite and cockroach, which both contain tropomyosin,^1,22 and the recently found cockroach proteins, vitellogenin, and arginine kinase.²³

We also determined that there was a statistically significant relationship between cockroach sensitization and grass mix, olive, pine, tree mix, weed mix, aspergillus, and dog dander. We suggest that an immunologic predisposition appears to be an important determinant in the development of multi-sensitization. In the literature, there is no previous report describing multiple sensitization linking cockroach and pine, aspergillus, or dog dander. The association we found appears not to be related to a cross reaction, but rather to multiple sensitizations in atopic patients. When we performed multivariable logistic regression analysis to these allergens, we found that there was a positive correlation with pine and aspergillus, and a negative correlation with mold mix and weed mix (Table 3).

The positive relationship between cockroach and pine sensitivity cannot be explained by molecular similarity. However, we speculate that this relation can result from the coexistence of pine pollen spread and the cockroach production period in spring time.

We also found a positive association between cockroach sensitization and aspergillus. There is no previous clinical study showing this relation. There is only 1 report describing multiple sensitizations between cockroach and a kind of fungi; alternaria.²⁴ Recently, Chuang et al.²³ identified a total of 10 new Blattella germanica IgE-binding proteins by using a combination of proteomic techniques and bioinformatic allergen database analysis. Among them, enolase, which is highly conserved (>80% homology) among homologs in other plants and fungi, has cross reactivity with Aspergillus fumigatus allergenic protein (Asp f 22).

Recent studies have shown that early exposure to cockroach allergens may contribute to the development of recurrent wheezing and asthma in early childhood. These findings and recommendations to reduce exposure to cockroach allergens can be helpful for susceptible children.¹⁹ Cockroach infestations are not easily eliminated within homes, schools, and buildings. However, with general cleaning practices and proven extermination techniques infestations can be brought under control. In addition, progress on molecular biology cloning of cockroach allergens may lead to the development of novel forms of immunotherapy, which can be used to prevent “asthma and allergic rhinitis.”

There are several strengths to our study. First, our data are derived from the largest sample size in childhood to date. Although the analysis was made retrospectively, the same physician applied the standard protocol to all patients. Our allergen panels included not only the common aeroallergens for our country, but also the unique ones for our geographic location, which enabled us to identify novel relationships with cockroach sensitivity in children.

In conclusion, we found that cockroach sensitivity is associated with the co-existence of “asthma and allergic rhinitis” in children. In addition, we found for the first time that there is a positive association between cockroach sensitization and pine and aspergillus allergens. Our study demonstrated that cockroach is a major allergen in children and recommend that it be routinely included in allergy skin test panels to diagnose cockroach sensitization.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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