Mite asthma in childhood: A study of the relationship between exposure to house dust mites and disease activity Shmuel Kivity, MD, Asher Solomon, MD, Ruth Soferman, MD, Yehuda Schwarz, MD, Kosta Y. Mumcuoglu, PhD,” and Marcel Topilsky, MD Tel Aviv and Jerusalem, Israel Background: Children with asthma are commonly sensitized to the house dust mite. Methods: We took monthly measurements from July to December of the amount of mites in the mattresses of asthmatic children and correlated them with symptom score, pulmonary function, and airway hyperreactivity to methacholine. Results: In spite of the high number of Dermatophagoides pteronyssinus throughout this period, symptom and treatment scores, as well as PC,, to methacholine, worsened during the months of September and October. Conclusions: It is concluded that when asthmatic children allergic to mites are exposed to high levels of mite allergen, the number of mites in the mattress dust no longer correlate with increased symptoms, and that other factors are more likely to be associated with exacerbation. (J ALLERGYCLINIMMUNOL 1993;91:844-9.) Key words: Bronchial asthma, mite count, methacholine PC,,, symptom score In many parts of the world, including Israel, pyr- oglyphid mites in house dust have been demonstrated as important allergens associated with bronchial asthma. I-4 Dermatophagoides pteronyssinus is the most widely distributed of the house dust mites-especially in humid areas.’ Dermatophagoides furinae is also present in these areas, but in smaller quantities.‘. 5 These two mites cross-react, as observed by skin test- ing and RAST assays.6 Patients are not usually aware of a direct relationship between bronchospasm and exposure to house dust.’ The role of mite in the patho- physiology of bronchial asthma has so far been gath- ered from studies of bronchial provocation to allergens in sensitive subjects,’ the correlation between numbers of mites in the home and disease state,’ the effect From the Institute of Pulmonary Disease and Allergy Unit, Tel- Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel- Aviv University, and the *Department of Medical Entomology, Hadassah Medical School, The Hebrew University of Jerusalem, Israel. Received for publication Nov. 18, 1991. Revised Oct. 28, 1992. Accepted for publication Oct. 28, 1992. Reprint requests: Shmuel Kivity, MD, Allergy Unit, Ichilov Hos- pital, Tel-Aviv Sourasky Medical Center, 6 Weizman St., Tel- Aviv 64239, Israel. Copyright 0 1993 Mosby-Year Book, Inc. 0091-6749193 $1.00 + .lO l/1/43832 844 Abbreviations used FEV,: Forced expiratory volume in I second PC,: Provocation dose of methacho- line inducing 20% drop in FEV, PEFR: Peak expiratory j?ow rate PEFR%: Mean difference in peak expi- ratory flow rate (in percent) be- tween morning and evening of decreasing the number of mites on disease activ- ity, KM* and demonstrations that mite allergen is more prevalent in patients with bronchial asthma.” We undertook to evaluate the relationship between mite number and different indexes of disease activity in children with bronchial asthma who are skin sen- sitive to mite only. PATIENTS AND METHODS Seventeen children who fulfilled the American Thoracic SocietyCriteria for ReversibleObstructive Airway DiseaseI were selected from patients of the Pulmonary Diseaseand Allergy Service at Ichilov Hospital, Tel-Aviv, Israel. Inclu- sion criteria were basedon the following: 1. Positive skin test (wheal size >5 mm mean diameter by puncture method) to D. farinae extract only 1 per 100
Transcript
Mite asthma in childhood: A study of the relationship between exposure to house dust mites and disease activity
Shmuel Kivity, MD, Asher Solomon, MD, Ruth Soferman, MD, Yehuda Schwarz, MD, Kosta Y. Mumcuoglu, PhD,” and
Marcel Topilsky, MD Tel Aviv and Jerusalem, Israel
Background: Children with asthma are commonly sensitized to the house dust mite. Methods: We took monthly measurements from July to December of the amount of mites in the mattresses of asthmatic children and correlated them with symptom score, pulmonary function, and airway hyperreactivity to methacholine. Results: In spite of the high number of Dermatophagoides pteronyssinus throughout this period, symptom and treatment scores, as well as PC,, to methacholine, worsened during the months of September and October. Conclusions: It is concluded that when asthmatic children allergic to mites are exposed to high levels of mite allergen, the number of mites in the mattress dust no longer correlate with increased symptoms, and that other factors are more likely to be associated with exacerbation. (J ALLERGYCLINIMMUNOL 1993;91:844-9.)
In many parts of the world, including Israel, pyr- oglyphid mites in house dust have been demonstrated as important allergens associated with bronchial asthma. I-4
Dermatophagoides pteronyssinus is the most widely distributed of the house dust mites-especially in humid areas.’ Dermatophagoides furinae is also present in these areas, but in smaller quantities.‘. 5 These two mites cross-react, as observed by skin test- ing and RAST assays.6 Patients are not usually aware of a direct relationship between bronchospasm and exposure to house dust.’ The role of mite in the patho- physiology of bronchial asthma has so far been gath- ered from studies of bronchial provocation to allergens in sensitive subjects,’ the correlation between numbers of mites in the home and disease state,’ the effect
From the Institute of Pulmonary Disease and Allergy Unit, Tel- Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel- Aviv University, and the *Department of Medical Entomology, Hadassah Medical School, The Hebrew University of Jerusalem, Israel.
Received for publication Nov. 18, 1991. Revised Oct. 28, 1992. Accepted for publication Oct. 28, 1992. Reprint requests: Shmuel Kivity, MD, Allergy Unit, Ichilov Hos-
pital, Tel-Aviv Sourasky Medical Center, 6 Weizman St., Tel- Aviv 64239, Israel.
Abbreviations used FEV,: Forced expiratory volume in I
second PC,: Provocation dose of methacho-
line inducing 20% drop in FEV, PEFR: Peak expiratory j?ow rate
PEFR%: Mean difference in peak expi- ratory flow rate (in percent) be- tween morning and evening
of decreasing the number of mites on disease activ- ity, KM* and demonstrations that mite allergen is more prevalent in patients with bronchial asthma.”
We undertook to evaluate the relationship between mite number and different indexes of disease activity in children with bronchial asthma who are skin sen- sitive to mite only.
PATIENTS AND METHODS
Seventeen children who fulfilled the American Thoracic Society Criteria for Reversible Obstructive Airway DiseaseI were selected from patients of the Pulmonary Disease and Allergy Service at Ichilov Hospital, Tel-Aviv, Israel. Inclu- sion criteria were based on the following: 1. Positive skin test (wheal size >5 mm mean diameter by
puncture method) to D. farinae extract only 1 per 100
Kivity et al. 845 J ALLERGY CLIN IMMUNOL VOLUME 91, NUMBER 4
TABLE I. Patient characteristics
Month of treatment be Mean FEV, Mean FVC
No. (vr) Sex Llsec (%.) L (%I Inh. salb. Th. St.
I 14 F 1.57 (65) 2.06 (85) 7,8,9,10 8,lO 10 2 13 F 1.52 (75) 1.76 (89) 7,10,12 7,lO - 3 12 M 2.20 (82) 2.82 (95) 8,9,10 10,ll 10 4 10 M 2.23 (85) 2.47 (86) 10,12 10,12 - 5 9 M 1.16 (71) 2.04 (95) 9.10 9,lO - 6 11 M 1.85 (82) 2.29 (88) 12 12 - 7 10 M 1.82 (83) 2.32 (83) 7,8,9,10,11,12 7,8,9,10 9,lO 8 14 M 1.86 (90) 2.10 (86) 9.10 - 9,lO 9 7 M 1.58 (85) 1.68 (91) 7,8,9,10,11 9,lO -
10 11 F 1.69 (75) 1.84 (93) 8,10,11 - - 11 10 M 1.53 (72) 2.02 (95) 7,8,10 8 - 12 13 F 1.66 (77) 2.37 (102) 9,lO 9,lO - 13 8 F 1.72 (91) 1.8 (95) 7,10,11 10 - 14 14 F 1.80 (77) 2.40 (95) 10 10 - 15 12 F 1.69 (70) 1.81 (89) 9.10 9,lO - 16 10 M 1.37 (69) 1.75 (99) 9,lO 9,lO 10 17 14 F 2.27 (98) 2.61 (101) 9,10,11 9,lO 9
Mean, Of all study days (before methacholine challenge); each number represents months during which therapy was given (7-July, &August, 9-September, IO-October, 1 l-November, 12-December); WC, forced with capacity; Inh. m/b.. inhaled salbutamol; Th., long-acting theophylline containing drugs; St., short course of prednisone (up to 1 week).
wtivol (Hollister-Stier Laboratories, Spokane, Wash.) among 23 other common allergens that include the fol- lowing: dust, mite, molds, epidermal, grasses, weeds, and trees;
2. Baseline forced expiratory volume in 1 second (FEV,) greater than 65% of predicted values;
3. Ability to cooperate with the study. None of the patients had any illness other than respiratory
allergic disease. Informed consent was obtained after approval by the local
Helsinki Committee.
Dust sampling and mite isolation
The parents were instructed not to vacuum the child’s mattress during a 6-month period, including 3 months before the study. The mattress was divided into six areas, and at the beginning of each month a different area was vacuumed by a hand-held vacuum cleaner fitted with a double-layer domestic tissue filter. The samples were stored in sealed plastic bags at 4” C before extraction and mite counting. The house dust was filtered through two sieves, placed one on top of the other, the upper with holes of 0.9 mm, and the lower with holes of 0.09 mm. Contents remaining on the lower sieve (mites and particles of similar size) were emptied into dichloromethane in which mites float, and the supernatant was passed through a filter with the aid of a vacuum pump. The last step was repeated three times. The filter containing the mites was immersed in lactic acid and then filtered again with black filter paper. The filter paper was examined under a dissecting microscope for the pres- ence of mites, which were removed and mounted on mi-
croscope slides with use of Hoyer’s medium. All isolated mites were counted, identified, and their number per gram of dust was calculated by an expert entomologist.
Spirometry was done with a Fukuda Spiro (Fukuda San- gyo Co., Ltd., Chiba, Japan) analyzer. Bronchial provo- cation with methacholine was performed according to the method of Chai et al. Is Provocation concentration, inducing 20% decrease in FEV, (PC,), was determined from each inhalation challenge. To minimize variability, an experi- enced technician performed the tests throughout the study. Peak flow rates were obtained with a Mini-Wright flow meter (Clement Clarke International, Harlow. U.K.) in the home.
Experimental protocol
Each child who participated in the study underwent methacholine inhalation challenge and dust sampling per- formed at the beginning of July, August, September, Oc- tober, and November, and in December in only eight patients (1 through 8).
Throughout the study the patients filled in symptom score forms that included the following data: (1) cough (0 to 3), (2) wheezing (0 to 3), (3) shortness of breath during the day and night (0 to 3), measurement of peak expiratory flow rates (PEFRs) done twice daily (the best of three measure- ments was recorded). and careful monitoring of the drug consumed.
Statistical analysis
Pearson correlation test was done between mite count and symptom score or symptom and treatment scores; mite count
846 Kivity et al.
TABLE II. Monthly parameters of disease activity (patients 1-5)
Patient Month 7 8 9 10
J ALLERGY CLIN IMMUNOL APRIL 1993
11 12
1
B. FEV, 1.21 1.84 1.95 1.29 1.65 1.72 PC*, 0.25 0.08 0.30 0.13 0.25 0.22 s. c. II84 50184 9184 46184 21184 lo/84 M. C. 1500 900 950 330 850 700 PEFR% 14 18 15 17 10 12
B. FEV,, Baseline FEV, L/set; S. C., symptom score; M. C., Mite count per gram of dust (mattress); PEFR, mean difference in peak expiratory flow rate (in percent) between morning and evening.
and the degree of airway hyperreactivity (PC,,); and PC,,, and symptom and treatment scores. Fisher’s multiple com- parison test was used to assess drug consumption during the different months.
RESULTS
Seventeen patients, eight females and nine males, age range 7 to 14 years (mean, 11.9 years), partici- pated and completed the study. All were from the Tel- Aviv city area on the Mediterranean, where outdoor humidity during July to December ranges between 80% and 90%.
In Table I a summary of the patients’ characteristics is given. During October, 13 patients received long- acting theophylline drugs, and five received short courses of corticosteroids. During September, seven patients were given long-acting theophylline drugs, and only three received a short course of steroids. As shown in Table II, disease activity was more pro- nounced during the month of October, as demon- strated by the mean symptom score, mean PC&, as well as the requirement for steroids. It also appears
that during the months of September and October some of our patients had severe attacks of asthma that required administration of corticosteroids. Such at- tacks were not observed during the other months, although salbutamol was consumed in the autumn by many of the patients. A statistically significant dif- ference was observed between the months of Octo- ber and September and the others (p < 0.05).
No correlation was seen between mite count and the following parameters: Baseline FEV,, PC&, PEFR, symptom score, or scores obtained from com- bining monthly symptoms plus treatment. Good cor- relation was seen between symptom score and PC,, (p < 0.02) and symptom score plus treatment score to PC,,. Although patients 3, 4, 6, 10, 11, and 17 had PC, values in the normal range in spite of ex- posure to a high mite count, at least one value was in the asthmatic range (< 16 mgidl). Nine different species were isolated from the house dust of 48 sam- ples, with relative frequency of 92.4% for D. ptero- nyssinus, and 6.5% for D. farinae, which was found in 52% of the samples.
Kivity et al. 847 J ALLERGY CLIN IMMUNOL VOLUME 91. NUMBER 4
TABLE II. (cont.) Monthly parameters of disease activity (patients 6-10)
More than 20 years ago it was already established that the secretion of the pyroglyphide mite is the single most important cause of respiratory allergy. ’ However, it is not yet fully understood how the patients inhale it and in what form (such as size of particle) it reaches the bronchi. The relationship between the mite number in the immediate environment (such as the mattress) and the degree of respiratory symptoms is also ob- scure. Nor is it clear whether there is an exposure dose above which mite numbers no longer adversely affect the airway response (maximal response). In ad- dition, what effect, if any, does a reduction in mite numbers have (from 2OOO/gm of dust to lOOO/gm, or even to lOO/gm of dust), or does only complete elimination of mites improve symptoms?
A study from DenmarkI maintained that mites in quantities larger than 10011gm of house dust (or 2 pg of the allergen/ lgm) should be regarded as a risk factor for bronchial asthma, whereas other studies suggest a level in the range of 100 to 500 mites/gm of dust as a maximal “acceptable contamination.” A
- - -
1.10 8.00 6184 1300
11
1.88 0.65
35184 850
9
1.82 1.20 2184 -
5
- - - - -
- - - - -
more recent study proposes that the quantity of mite allergen in the first year of life is a good predictive value for the subsequent development of asthma at age 11 years. I7 Children with active wheeze had been exposed to more than 10 pg D . pteronyssinus per gram of dust in infancy. This amount is equivalent to 500 mites per gram of dust.
In the few studies done in warm and humid areas,’ the number of mites in the dust was usually greater than 5OO/gm. Therefore it was surprising that our patients did not have daily symptoms of dust asthma. In spite of the fact that the mean monthly mite number in the mattress of children with asthma in Tel-Aviv is greater than 2OOO/gm of dust, almost all the patients had exacerbation of their illness during the month of October. These attacks may be caused by increased exposure to respiratory viruses rather than by exposure to mites, numbers of which remained unchanged. Other causes should also be considered, although our patients were only mite sensitive. In spite of the fact that D. pteronyssinus was the predominant mite, others were also isolated. A high degree of cross-
848 Kivity et al. J ALLERGY CLIN IMMUNOL APRIL 1993
TABLE II. (cont.) Monthly parameters of disease activity (patients 1 I-15)
Patient Month 7 9 9 10 11 12
B. FEV,
11 PC20 s. c. M. C. BEFR%
1.56 1.45 1.60 1.38 1.10 0.35 30.00 17.00
15/84 28184 8/84 5184 1200 1300 1900 1100
14 18 9 5
12
B. FEV, 1.72 1.60 1.72 1.68 PC*, 0.34 0.22 0.40 0.18 s. c. 21184 25184 28184 21184 M. C. 2200 1800 1080 2200 &FR% 21 17 12 19
B. FEV, 1.64 1.76 1.75 1.79 0.45 7.00 0.40 0.35
20184 3184 15/84 30/84 2540 5460 3680 3500
24 14 23 21
13 PC*, s. c
14
M. C. BEFRS
B. FEV, 2.15 1.76 1.84 1.48 &I 0.10 0.30 0.35 0.06 s. c. 20184 10184 10184 60184 M. C. 3680 2800 2500 1580 &FR% 14 17 21 25
1.32 21.00 - 4184 -
2500 - 8 -
1.75 - 0.35 - 5184 -
2500 - 17 -
1.80 - 0.30 -
20/84 - 2800 -
19 -
1.60 0.30 -
20184 - 1000 -
19
B. FEV, 1.60 1.64 1.72 1.76 1.64 - PC,, 0.35 0.55 0.40 0.21 0.48 - s. c. 8184 lo/84 15/84 18/84 8184 - M. C. 1060 - 860 1500 1000 - @EFR% 22 16 15 19 15 -
sensitivity is known to exist between D. pteronyssinus and D. furinae,6 justifying the use of D. pteronyssinus for skin testing in these patients.
Other species of pyroglyphidae, as well as mites from the families glycyphadidae and cheyletidae, were also isolated. These may be of importance in certain patients, having a greater impact on disease activity than D. pteronyssinus or D. farinae. A similar analysis of dust mites in Israeli homes was reported by Feldman-Muhsam et al.* Here again, it is seen that the degree of airway hyperreactivity as established by methacholine challenge, correlates very well with symptom score or with mean monthly PEFR%, both of which seem to worsen during the month of October. It was interesting to note that in certain patients PC, to methacholine was not always in the accepted asth- matic range (I 16 mg/ml), and this could be due to the fact that they were not in an active state of their illness, because in all of them PC*,, decreased when they were symptomatic.
No correlation was seen between PC, methacholine and mite number, either for each patient or for the
group as a whole. It can be argued that sampling mites from the mattress is not the only source of exposure at home, and other areas should also be sampled. However, because mites were shown to be present in larger quantities in the mattress than in other areas at home,2 and because the patients spend between 8 to 10 hours per day in bed, one can assume that it more accurately represents natural exposure to mites.
Another issue that requires clarification is whether recurrent transient rise in the number of mites in the air (such as by wind, ventilation, home activity) is not more important in inducing an attack than the mite level in the mattress.
Tovey et al. ” showed that antigen P, in undisturbed air was generally very low, but after disturbance it increased 15fold. Price et al. I9 found no correlation between D. pteronyssinus in the carpets and the level in the air. They suggested that airborne antigen ex- posure is better related to sensitization. It is also likely that airborne exposure correlates better with disease activity. The impact of these observations needs fur- ther investigation.
J ALLERGY CLIN IMMUNOL VOLUME 91. NUMBER 4
Kiviiy et al. 949
TABLE II. (cont.) Monthly parameters of disease activity (patients 16 and 17)
One can conclude that although mite is a very im- portant allergen associated with bronchial asthma, when exposure occurs to high levels of mite allergen (i.e., maximal exposure), the number of mites in the mattress dust no longer correlates with exacerbation, and other factors (e.g., viral respiratory infections) are more likely to be associated with increased symptoms.
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