Asthma hospitalizations continue to decrease in schoolchildren but hospitalization rates for wheezing illnesses remain high in young children.

AIM: To analyse changes in hospitalization rates for asthma in children during recent years. METHODS: In a population-based analysis, changes in asthma hospitalization rates were studied in children in Göteborg (Gothenburg), the second largest city in Sweden, during 1985-2000. The changes in different age groups have been correlated with the delivery of inhaled corticosteroids to the age groups. RESULTS: In the 5 to 18-y age group, there was a continuous, significant decrease in number of hospital days, admissions and individual patients admitted for asthma not only for the entire study period, 1985-2000, but also during the past 10-y period. The number of hospital days in the year 2000 was only 6% of the figure for 1985. An inverse correlation between delivery of inhaled corticosteroids and hospitalization for asthma was seen not only during 1985-1995, when use of inhaled corticosteroids became widespread (r(s) = -0.95, p = 0.007 for hospital days), but also when the entire period from 1985 to 2000 was analysed. Conversely, in the 0 to 1-y and 2 to 4-y age groups, there was no decrease in hospitalizations for wheezing illnesses or asthma-like symptoms during the past 10-y period, 1991-2000. CONCLUSION: During the period 1985-2000 the number of hospital days owing to asthma decreased by more than 90% in the 5 to 18-y age group. The marked decrease in asthma hospitalization rates among schoolchildren represents a great advance in paediatric respiratory medicine, which has been continuous during the past 10-y period. However, in young children admissions for wheezing have apparently not decreased.

Topical steroid treatment of allergic rhinitis decreases nasal fluid TH2 cytokines, eosinophils, eosinophil cationic protein, and IgE but has no significant effect on IFN-gamma, IL-1beta, TNF-alpha, or neutrophils.

BACKGROUND: Topical treatment with glucocorticoids (GCs) is known to decrease eosinophils but not neutrophils in patients with allergic rhinitis. OBJECTIVE: We sought to examine whether the differential effects of GC treatment on eosinophils and neutrophils are mirrored by differential effects on T(H)1/T(H)2 cytokines and the neutrophil-associated cytokines IL-1beta and TNF-alpha. METHODS: Differential counts of eosinophils and neutrophils in nasal fluids from 60 children with seasonal allergic rhinitis treated with a topical GC were examined after staining with May-Grünwald-Giemsa stain. Nasal fluid levels of IFN-gamma, IL-4, IL-6, IL-10, IL-1beta, and TNF-alpha were examined with ELISA, and IgE and eosinophil cationic protein (ECP) levels were examined with RIA. RESULTS: After GC treatment, there was a statistically significant decrease of the T(H)2 cytokines IL-4, IL-6, and IL-10, as well as ECP and IgE. By contrast, there were no significant changes of the levels of IFN-gamma, IL-1beta, TNF-alpha, or neutrophils. In the GC-treated patients IL-1beta and TNF-alpha levels correlated with neutrophils and ECP, and IL-1beta correlated with eosinophils. Furthermore, ECP correlated with both eosinophils and neutrophils. Neither IL-1beta nor TNF-alpha correlated with IgE. Patients with high neutrophil counts after GC treatment were found to have significantly higher eosinophil counts and ECP than patients with low counts. CONCLUSIONS: The beneficial effects of topical treatment with GC in patients with allergic rhinitis could be attributed to downregulation of T(H)2 cytokines, with an ensuing decrease of eosinophils, ECP, and IgE. It is possible that neutrophils could counteract the beneficial effects of GCs by releasing the proinflammatory cytokines IL-1beta and TNF-alpha.

Increase of the soluble IL-4 receptor (IL-4sR) and positive correlation between IL-4sR and IgE in nasal fluids from school children with allergic rhinitis.

Soluble cytokine receptors (SCR) can either act as inhibitors, by competitively inhibiting cytokines from binding to their membrane-bound receptors, or as enhancers, by serving as cytokine carriers. We have previously found that the levels of the Th2 cytokines interleukin (IL)-4, IL-5, IL-6, and IL-10 were positively correlated to eosinophils and IgE in nasal fluids from 60 children with seasonal allergic rhinitis. In this study, nasal fluids were reexamined to analyze IL-4sR, IL-6sR, IL-1 beta, TNF-alpha, IL-1sR2, TNF-sR1, and TNFsR2 in relation to eosinophils, neutrophils, ECP, and IgE. In allergic patients IL-4sR increased significantly during the pollen season, and weak, but positive correlations with IgE and eosinophils were found (r = 0.45, P < 0.001 and r = 0.4, P < 0.001 respectively). By contrast, none of the other SCR showed increases or correlations with IgE. However, positive correlations between IL1 beta, TNF-alpha, IL-6sR, IL-1sR2, TNF-sR1, TNF-sR2, and either neutrophils or ECP were found. Also, in healthy controls, these cytokines and their receptors were positively correlated to neutrophils or ECP. Thus, increased levels of the soluble IL-4 receptor, as well as IgE, were specifically associated with allergic rhinitis, whereas all other SCR correlated with either inflammatory cells or their products, in both allergic and healthy subjects. These results may suggest that SCR in vivo act as cytokine enhancers, rather than inhibitors.

Low levels of interferon-gamma in nasal fluid accompany raised levels of T-helper 2 cytokines in children with ongoing allergic rhinitis.

The T-helper 2 (Th2) cytokines interleukin-(IL-) 4, IL-5, IL-6, IL-10 and the Th1 cytokine IFN-gamma and their associations with eosinophil, eosinophil cationic protein (ECP) and immunoglobulin (Ig) E were studied in nasal lavage fluid from 60 school children with allergic seasonal rhinitis and 36 nonatopic healthy controls, before and during the pollen season. Eosinophil differential counts and IgE increased significantly in the patients during the pollen season. The eosinophil differential counts, ECP and IgE were all significantly higher during the season than in specimens simultaneously obtained from the nonatopic controls. Before season, the levels of ECP and IgE, but not eosinophils, were significantly higher in the patients than in the controls. During the season the nasal lavage fluid levels of IFN-gamma were significantly lower and the IL-4/IFN-gamma quotients significantly higher in the allergic than in the control children. In the allergic children, but not in the controls, the nasal fluid levels of the Th2 cytokines IL-4, IL-5 and IL-10 increased during the season, and together with IL-6, were correlated with the differential counts of eosinophils, and with the levels of ECP and IgE. These findings are compatible with the hypothesis that a deficient release of the Th1 cytokine IFN-gamma plays an important role in the pathogenesis of allergic inflammation. Regardless of whether the defective IFN-gamma secretion is primary or a consequence of suppression by other cytokines, it will in the atopic subjects enhance the release of Th2 cytokines, which in turn will facilitate the development of allergic inflammation.

Interleukin-5 and interleukin-8 in relation to eosinophils and neutrophils in nasal fluids from school children with seasonal allergic rhinitis.

The objectives of this study were to measure interleukins 5 and 8 (IL-5 and IL-8) in relation to eosinophils and neutrophils, in nasal lavage fluids from 60 school children with allergic rhinitis, and to determine the influence of treatment with a topical steroid (budesonide) on the levels of the two cytokines. Highly sensitive enzyme immunoassays were used to analyze IL-5 and IL-8. IL-5 levels and relative eosinophil counts in nasal lavage fluid increased significantly in patients with allergic rhinitis during the pollen season, compared with values obtained before the start of the season, and decreased significantly after treatment with budesonide. By contrast, no significant changes in IL-8 or neutrophils were found during the pollen season, nor did they decrease following treatment. In the untreated patients, IL-5 levels correlated significantly with eosinophil counts but not with neutrophil counts, whereas IL-8 levels correlated with neutrophil counts but not with eosinophil counts. After budesonide treatment, the correlation between IL-8 and neutrophils remained, and a correlation between IL-8 and eosinophils emerged. These findings support the concepts that IL-5 has a key role in regulating eosinophils and that IL-8 is important for the regulation of neutrophils. Whereas IL-5 and relative eosinophil counts are profoundly affected by topical steroid treatment, IL-8 and neutrophils are not demonstrably affected by such treatment. It is possible that neutrophils, through the release of IL-8, could be chemotactic for eosinophils in steroid-treated patients.

[Why is the prevalence of allergy increasing? Changed microbial load is probably the cause]. / Varför ökar allergiprevalensen? Förändrad mikrobiell belastning troligaste orsaken.

The prevalence of allergic disease is increasing dramatically in industrialised countries. Environmental factors that are putative causes of this increase are to be sought among those that induce a shift in T-helper cell (Th1/Th2) balance toward Th2 immunity dominance, and whose natural occurrence is consistent with epidemiological evidence of regional differences in allergy prevalence. Of such factors, changes in the panorama of bacterial and viral infections, altered intestinal microflora, and changes in dietary habits (particularly increased consumption of omega-6 fatty acids) seem to be the most likely causes of the increased prevalence of allergic diseases. There are also other factors, however, such as diesel exhaust particles, tobacco smoke and environmental toxins, which may partly fulfil the immunological and epidemiological criteria. As several of these putative environmental factors exert powerful effects in vitro, the increase in allergy prevalence is hardly surprising.

Prevalence of allergy in children in relation to prior BCG vaccination and infection with atypical mycobacteria.

By influence on the Th1/Th2 cell balance, infectious agents may affect the development of atopic allergy. In this study, we investigated whether previous BCG vaccination or infection with atypical mycobacteria might be related to the development of atopic disease. The study, which involved skin testing with mycobacteria and answers to a questionnaire for more than 6000 children in Sweden, revealed a low prevalence of allergy among BCG-vaccinated children who were immigrants or adopted from other countries. Vaccinated children born in Sweden, however, did not have significantly lower allergy prevalence than age-matched, unvaccinated children. Furthermore, the overall frequencies of skin-test reactivity to the atypical mycobacteria M. avium and M. scrofulaceum were higher rather than lower in allergic than in nonallergic children. By contrast, there was a tendency toward a lower frequency of more strongly positive skin reactions (> or = 10 mm) to mycobacteria in allergic than in nonallergic children. These findings do not support the hypothesis that early mycobacterial infections have a suppressive effect on the development of atopic disease. Earlier findings of an apparent association between atopy and lack of previous mycobacterial infection may possibly be explained by a relatively decreased ability of atopic patients to mount strong Th1 cell-mediated immune responses.

Cytokines in nasal fluids from school children with seasonal allergic rhinitis.

Allergic rhinitis is a particularly good model for studies of cytokine production in vivo. In this study the occurrence of the cytokines IL-4, IL-5, IL-10 and IFN-gamma as well as the soluble receptor for IL-4 in nasal lavage fluids were assayed in 38 school children, with seasonal allergic rhinitis, and 19 healthy age-matched, non-atopic controls, using highly sensitive enzyme immunoassays. IL-4 levels in patients with seasonal allergic rhinitis were markedly increased in comparison with those in non-atopic controls or in atopic patients before the start of the pollen season. In controls, but not in the atopic patients, levels of IFN-gamma and IL-5 were significantly higher in specimens obtained during the pollen season than in those obtained outside the season. The IL-4/IFN-gamma ratios were significantly higher in atopic than in non-atopic subjects and further increased in atopic patients during the season. In addition to IL-4, elevated levels of IL-10 were observed in association with seasonal rhinitis. Following treatment with a topical steroid (budesonide) there was a statistically significant increase of the levels of soluble IL-4 receptor. These findings indicate that nonatopic and atopic individuals react to pollen exposure with distinct cytokine patterns in agreement with the Th1/Th2 concept. Topical steroids may possibly decrease inflammation by increasing the formation of soluble IL-4 receptor.

Inflammatory markers in childhood asthma.

The importance of airway inflammation in the pathogenesis of asthma is clearly established. Studies in adults as well as in children have led to the concept that asthma is a chronic inflammatory disease. Airway inflammation is found even in mild asthma. Bronchoconstriction and hyper-reactivity appear to be secondary to the release of inflammatory mediators. The changed view of the pathogenesis of asthma and current emphasis on anti-inflammatory treatment have raised a need for markers that reflect the inflammatory status in the airways. This is of special importance in paediatric practice because lung function tests are less easily performed in young children, and it is preferable to keep steroid doses as low as possible. The eosinophil granulocyte has a multitude of proinflammatory functions and plays a key role in the asthmatic inflammation. It secretes toxic proteins and produces cytokines, which have important roles in airway inflammation. Use of eosinophil granula proteins to monitor inflammation is now finding its place. Measurement of eosinophil cationic protein (ECP) seems to be a valuable complement to the recording of lung function. For paediatric use, measurement of urinary eosinophil protein X (EPX) is promising because it does not require blood sampling.

Urinary eosinophil protein X in children with atopic asthma: a useful marker of antiinflammatory treatment.

BACKGROUND: Bronchial asthma is associated with elevated serum levels of eosinophil products, such as eosinophil protein X (EPX), but the occurrence in urine of this substance in patients with asthma has not previously been studied. OBJECTIVE: This study was performed to clarify whether increased amounts of eosinophil granulocyte proteins in urine and serum reflect ongoing asthmatic inflammation and whether decreasing values reflect successful treatment. METHODS: Twelve children with a median age of 12.5 years who had mild or moderate atopic asthma were studied for 3 months. At the time of inclusion in the study, treatment with inhaled budesonide was initiated. Nine children of the same age without atopic disease served as control subjects. Levels of EPX, eosinophil cationic protein (ECP), and myeloperoxidase in serum and in urine (urinary EPX) were determined at inclusion and then after 3 months of treatment. Spirometry was performed on the same occasions. RESULTS: At the time of inclusion, urinary EPX and serum ECP were significantly higher in children with atopic asthma than in the control subjects (mean, 116.4 vs 43.0 micrograms/mmol creatinine [p = 0.004] and 37.0 vs 14.8 micrograms/L [p = 0.004]). In the asthma group urinary EPX, as well as serum ECP, decreased significantly after 3 months of treatment with budesonide (116.4 to 68.4 micrograms/mmol creatinine [p = 0.005] and 37.0 to 24.0 micrograms/L [p = 0.04]). At the same time, peak expiratory flow values increased significantly in the children with asthma (76.0% to 87.8% of predicted value [p = 0.005]) but not in the control subjects (87.0% to 90.1%). In the asthma group the levels of myeloperoxidase were similar to those in the control group, both at inclusion and after 3 months. CONCLUSION: Increased urinary EPX and serum ECP levels seem to reflect active atopic asthma, whereas decreased levels after antiinflammatory treatment probably reflect normalization of airway inflammation, and indirectly, improved lung function.

Decrease in hospitalization for treatment of childhood asthma with increased use of antiinflammatory treatment, despite an increase in prevalence of asthma.

BACKGROUND: During the past 15 years, the prevalence of asthma in children in Sweden has doubled. However, since 1985, antiinflammatory treatment with inhaled steroids has increased continuously. OBJECTIVE: The aim of this study was to analyze the net effect of these changes in terms of hospitalization of children for treatment of asthma. METHODS: The numbers of hospital days, admissions, and individual patients admitted to the Children's Hospital in Göteborg because of acute asthma were recorded from 1985 through 1993. all the in-patient treatment of children is centralized at this hospital (i.e., the study was population-based). Göteborg has half a million inhabitants. Hospitalization policies were not altered during the study period. RESULTS: In children aged 2 to 18 years, the number of hospital days per year gradually decreased to less than a third (r = 0.9; p less than 0.001), and admissions decreased by 45% (r = 0.7; p less than 0.05). The decrease in hospitalization was most marked in the group older than the age of 5 years in which hospital days were reduced to one fifth (r = 0.9; p less than 0.0001) and admissions were halved (r = 0.8; p less than 0.05). A decreasing trend in number of hospital days was also seen in the 2- to 5-year-old group. The number of individual patients admitted did not show a statistically significant decreasing trend. In children under the age of 2 years, the number of hospital days fluctuated, and there was no clear-cut change with time. CONCLUSION: Although increased concentration on the education of parents and patients may have been a contributing factor, the major reason for the decrease in hospitalization in the group of children aged 2 to 18 years is most probably antiinflammatory treatment with inhaled steroids. The results suggest that this is a very cost-effective therapeutic approach.

Leukotriene B4 and C4 generation by human leukocytes after ex vivo stimulation with Ca-ionophore and opsonized zymosan in children with atopic asthma.

The ex vivo release of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) from leukocytes was evaluated after stimulation with both Ca-ionophore (Ca-I) and opsonized zymosan (OZ) in children with atopic asthma. Twenty-seven patients with asthma of varying severity were evaluated and divided into three groups: 1) moderate to severe asthma using inhaled steroids and symptom-free for the last 3 weeks (n = 8), 2) mild asthma with sporadic symptoms, only using inhaled beta 2-agonists < 3 times/week (n = 8), and 3) acute asthmatic attacks admitted to hospital (n = 11). A group of children without atopic disease or any other known disease served as controls (n = 15). Total serum IgE levels were significantly increased in the children with asthma compared with the control group. LTC4 production was only significantly increased in the group of children with moderate to severe asthma after stimulation with Ca-I, when compared with controls. In the same group, a trend towards increased LTC4 production after stimulation with OZ was found. LTB4 was not significantly increased in any patient group compared with the control group. A significant correlation between LTC4 production after stimulation with Ca-I, but not OZ, and the relative blood eosinophil count was found in all subjects. LTC4 generation per eosinophilic cell after stimulation with Ca-I or OZ was not statistically different in any patient group compared with the controls. We conclude that the increased leukotriene (LT) levels found after the stimulation of peripheral white blood cells sampled from atopic children with asthma are mainly the result of increased numbers of LT-producing cells, rather than due to increased releasability from these cells.

The prevalence of childhood asthma in Costa Rica.

The prevalence of asthma in children between the ages of 5 and 17 years in Costa Rica was determined using a large sample (n = 2682). The definition of asthma was based on a combination of a physician's diagnosis and a symptom score, using information from a questionnaire given to the parents. An overall asthma prevalence as high as 23.4% was found. Sex, age, urban/rural location, or rain precipitation did not show any association with the diagnosis of asthma. The presence of smokers in the home was found to be an important risk factor (odds ratio = 1.6). Another identified risk factor was a high yearly average outside temperature, i.e. above 25 degrees C (odds ratio = 1.8). Furthermore, the proportion of children with more than four upper respiratory infections during the preceding year was found to be significantly increased in children with asthma (odds ratio = 4.3). The non-asthma group seemed to use equal amounts of drugs for the treatment of asthma as the asthma group. For a country like Costa Rica with limited economic resources the current work indicates two important issues for consideration in the future; firstly, to try to define the cause(s) of asthma and secondly, to continuously inform the physicians about the best way of diagnosing and treating asthmatic patients to ensure optimal handling of this large patient group.

Eosinophil cationic protein, myeloperoxidase and tryptase in children with asthma and atopic dermatitis.

Serum levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, total IgE and differential blood cell counts were studied in atopic children with: 1) moderate to severe asthma using inhaled steroids and symptom-free for the last 3 weeks (n = 13), 2) mild asthma with sporadic symptoms, using only inhaled beta 2-agonists < 3 times/week (n = 15), 3) acute asthmatic attacks admitted to hospital (n = 12), 4) mild to moderate atopic dermatitis (n = 14). Fifteen children without any history of atopy served as controls. ECP, MPO, tryptase and IgE were measured in serum by radioimmunoassays (RIA). The symptom-free children with inhaled steroids had similar median ECP and MPO values as the controls, 8.0 and 360 micrograms/l, vs. 9.0 and 310 micrograms/l, while both ECP and MPO were significantly (p < 0.001) increased in the symptom-free children without anti-inflammatory treatment, 32 and 887 micrograms/l and in those with acute asthma, 28 and 860 micrograms/l. The children with atopic dermatitis had increased ECP but normal MPO levels, 16.0 and 455 micrograms/l. Tryptase in serum was not measurable in any patient. All groups except the control group had significantly elevated total IgE levels. The results indicate that in atopic children serum ECP is a good marker of ongoing asthma or atopic dermatitis. The normal levels of ECP and MPO in the children with asthma using inhaled steroids seem to reflect successful anti-inflammatory treatment. The increased levels of ECP and MPO in the children with mild asthma and no anti-inflammatory treatment may indirectly reflect airway inflammation.

Palpable lymph nodes of the neck in Swedish schoolchildren.

We studied 3592 Swedish schoolchildren, 8 or 9 years old, examined for palpable submandibular, cervical and supraclavicular lymph nodes. All children were skin tested with 2 TU PPD RT23 and with 0.1 microgram of Mycobacterium avium sensitin or 0.1 microgram of M. scrofulaceum sensitin. A total of 991 children had palpable lymph nodes in any of the three locations. Among them, 811 had lymph nodes in one location, 162 in two locations and 18 in three. In 312 children, the lymph nodes were > or = 5 mm in size in any location. The most common location was submandibular. Boys had a significantly higher prevalence of palpable lymph nodes than girls. There was also seasonal variation. Children infected by atypical mycobacteria (sensitin reaction > or = 6 mm) did not have a higher prevalence of palpable lymph nodes than those not infected.

Leukotriene B4 and C4 generation by blood leukocytes after ex vivo stimulation by Ca-ionophore and opsonized zymosan in children with atopic dermatitis.

The ex vivo release of leukotrienes B4 (LTB4) and C4 (LTC4) from the leukocytes of children with atopic dermatitis (AD) was evaluated after stimulation with Ca-ionophore and opsonized zymosan and compared with that of control children of similar ages. The blood eosinophil counts and total serum IgE levels in AD children were significantly higher than those in control children. The production of LTC4, but not LTB4, was significantly higher in AD children than in control children. There was a significant correlation between the relative blood eosinophil count and LTC4 generation after stimulation with both Ca-ionophore and opsonized zymosan in all subjects. Calculations of the amount of LTC4 produced per eosinophilic cell showed that there was no significant difference between cells from AD children and control children in terms of their ability to produce LTC4. These findings suggest that the enhanced LTC4 generation is due to increased numbers of eosinophils rather than to enhanced releasability of these cells.

Nebulised racemic adrenaline in the treatment of acute bronchiolitis in infants and toddlers.

The effect of inhaled nebulised racemic adrenaline upon symptoms of acute bronchiolitis was investigated in 29 infants and toddlers aged 2-17.5 months by transcutaneous oxygen tension (TcPO2), oxygen saturation, transcutaneous carbon dioxide tension (TcPCO2), and clinical evaluation in a double blind placebo controlled study. Clinical score and TcPO2 improved significantly at 30, 45, and 60 minutes after inhalation of racemic adrenaline, with an increase in TcPO2 > or = 0.5 kPa in 72% of the children < 1 year of age. No significant improvement was observed after inhalation of placebo. No significant changes in heart rate or TcPCO2 were observed from before to after inhalation, but a small increase in mean systolic blood pressure was observed immediately and 45 minutes after racemic adrenaline inhalation. This study demonstrates that treatment with nebulised racemic adrenaline improved oxygenation and clinical signs in hospitalised children aged less than 18 months with bronchiolitis.

Pityrosporum ovale and atopic dermatitis in children and young adults.

Children aged 0-21 years, 60 children with atopic dermatitis (AD), 40 children with rhinoconjunctivitis and or asthma (RA) and 40 children with no atopic history (HC) were studied to evaluate the relationship between skin colonisation with Pityrosporum ovale and the occurrence of specific IgE antibodies to P. ovale. The following studies were done: culture for P. ovale, measurement of IgE antibodies to P. ovale (skin prick test, RAST), Candida albicans, and Cladosporium herbarum (RAST) and IgG antibodies to P. ovale. P. ovale could be cultured with about the same frequency in children and young adults with AD and age-matched children with or without other atopic manifestations. In spite of similar colonisation, IgE antibodies against P. ovale occur only in atopy and more frequently in children with AD than in those with other types of atopic disease.

Sensitivity to sensitins and tuberculin in Swedish children. I. A study of schoolchildren in an urban area.

Non-BCG-vaccinated schoolchildren (8 or 9 years of age) were simultaneously tested on separate arms with 2 IU PPD RT23 and 0.1 microgram Mycobacterium avium sensitin RS10 or 0.1 microgram Mycobacterium scrofulaceum sensitin RS95. None of the 2819 analysed children had any known exposure to tuberculosis. A total of 3.4% reacted with an induration greater than or equal to 6 mm to PPD RT23. Half the number of children were tested with M. avium sensitin and 25.4% reacted while the remaining were tested with M. scrofulaceum sensitin and 32.4% reacted when the cut-off was 6 mm. For about 90% of the children the sensitin reaction was larger than or equal to the tuberculin (PPD RT23) reaction. Correlation analyses showed that moderate and high PPD RT23 values were combined with still higher sensitin values, indicating that the tuberculin reactions were mainly cross-reactions due to the antigenic similarity between tuberculin and sensitins. The presence of birds, dogs and cats in the homes was combined with an increased frequency of children reacting to the sensitins used. The children with reactions to PPD RT23 greater than or equal to 6 mm were examined and chest X-rays were performed. None of them showed any signs or symptoms of mycobacterial disease. In non-BCG-vaccinated Swedish schoolchildren without clinical signs of tuberculosis and without known contact with a contagious tuberculous person, indurations less than 12 to 14 mm on tuberculin testing are probably caused by atypical mycobacteria. In such cases sensitin tests should be performed to verify the suspicion.