Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.

The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL.

Exhaled nitric oxide in a population-based study of asthma and allergy in schoolchildren.

Exhaled nitric oxide (NO) reflects inflammation in the lower airways and is well adapted for use in children. The aims of this study were to investigate the distribution of the fraction of expired NO (FENO) in school children and to compare FENO and spirometry in relation to the International Study of Asthma and Allergies in Childhood questionnaire. The study was performed in 959 randomly selected 13-14-year-old school children in Uppsala, Sweden. Exhaled NO was measured at an inhalation rate of 0.1 l/s (FENO0.1) and a spirometric test was performed and data from these measurements were related to questionnaire data. Exhaled NO was measured according to American Thoracic Society recommendations, except the use of a mouth wash and an exhalation flow rate of 0.1 l/s. The distribution of the mean FENO0.1 values was skewed, with a preponderance of very low levels and a widespread tail of values ranging up to 102 parts per billion (ppb). Boys exhibited significantly higher mean FENO0.1 values than girls, 5.2 (4.7-5.7) vs 4.4 (4.0-4.8) ppb (geometric mean and 95% CI), P <0.01). Children who reported wheezing in the last year had higher FENO0.1 values than children that had not, 8.5 (7.1-10.2) vs 4.3 (4.0-4.6) ppb, P <0.001). The same association was found to most symptoms indicating hay fever and eczema. In contrast to this, only weak or inconsistent associations were found between asthma and spirometric indices. Exhaled NO levels were found to be independently related to male gender, wheeze and rhinoconjuctivitis but not to current eczema. In conclusion, exhaled NO was closely associated with reported asthma and allergy symptoms whereas spirometric indices such as percent predicted forced expiratory volume in 1 s were not. As most asthma cases in a population are mild, the findings suggest that exhaled NO is a sensitive marker of asthma and allergy.

NO2, as a marker of air pollution, and recurrent wheezing in children: a nested case-control study within the BAMSE birth cohort.

AIMS: To investigate the association between air pollution, including with NO2, and recurrent wheezing during the first two years of life. METHODS: A birth cohort (BAMSE) comprised 4089 children, for whom information on exposures, symptoms, and diseases was available from parental questionnaires at ages 2 months, and 1 and 2 years. NO2 was measured during four weeks in and outside the dwellings of children with recurrent wheezing and two age matched controls, in a nested case-control study (540 children). RESULTS: Conditional logistic regression showed an OR of 1.60 (95% CI 0.78 to 3.26) among children in the highest quartile of outdoor NO2 exposure in relation to those in the lowest quartile, adjusted for potential confounders. The corresponding OR for indoor NO2 was 1.51 (95% CI 0.81 to 2.82). An interaction with environmental tobacco smoke (ETS) was indicated with an OR of 3.10 (95% CI 1.32 to 7.30) among children exposed to the highest quartile of indoor NO2 and ETS. The association between NO2 and recurrent wheezing appeared stronger in children who did not fulfil the criteria for recurrent wheezing until their second year. CONCLUSIONS: Although the odds of increased recurrent wheezing are not statistically significantly different from one, results suggest that exposure to air pollution including NO2, particularly in combination with exposure to ETS, increases the risk of recurrent wheezing in children.

Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort.

INTRODUCTION: There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results. OBJECTIVE: To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study. METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders. RESULTS: A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38). CONCLUSION: Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.

Breast feeding and allergic diseases in infants-a prospective birth cohort study.

AIMS: To investigate the effect of breast feeding on allergic disease in infants up to 2 years of age. METHODS: A birth cohort of 4089 infants was followed prospectively in Stockholm, Sweden. Information about various exposures was obtained by parental questionnaires when the infants were 2 months old, and about allergic symptoms and feeding at 1 and 2 years of age. Duration of exclusive and partial breast feeding was assessed separately. Symptom related definitions of various allergic diseases were used. Odds ratios (OR) and 95% confidence intervals (CI) were estimated in a multiple logistic regression model. Adjustments were made for potential confounders. RESULTS: Children exclusively breast fed during four months or more exhibited less asthma (7.7% v 12%, OR(adj) = 0.7, 95% CI 0.5 to 0.8), less atopic dermatitis (24% v 27%, OR(adj) = 0.8, 95% CI 0.7 to 1.0), and less suspected allergic rhinitis (6.5% v 9%, OR(adj) = 0.7, 95% CI 0.5 to 1.0) by 2 years of age. There was a significant risk reduction for asthma related to partial breast feeding during six months or more (OR(adj) = 0.7, 95% CI 0.5 to 0.9). Three or more of five possible allergic disorders-asthma, suspected allergic rhinitis, atopic dermatitis, food allergy related symptoms, and suspected allergic respiratory symptoms after exposure to pets or pollen-were found in 6.5% of the children. Exclusive breast feeding prevented children from having multiple allergic disease (OR(adj) = 0.7, 95% CI 0.5 to 0.9) during the first two years of life. CONCLUSION: Exclusive breast feeding seems to have a preventive effect on the early development of allergic disease-that is, asthma, atopic dermatitis, and suspected allergic rhinitis, up to 2 years of age. This protective effect was also evident for multiple allergic disease.

Environmental risk factors for allergy and socioeconomic status in a birth cohort (BAMSE).

Associations between parental educational level and possible risk factors for atopic disease during the first months of life were explored in a cohort of 4089 neonate children born 1994-96 in Stockholm, Sweden. Reports concerning a number of life style factors during pregnancy and after the baby was born were obtained by questionnaire. There was a strong negative association between duration of education and maternal smoking during pregnancy, parental smoking after the baby was born and keeping of cat and dog (p-trend < 0.001), respectively. For example, smoking during pregnancy was reported by 6.7% (95% CI 5.5-7.9) of mothers with college or university degree and by 22.2% (95% CI 20.1-24.5) of those with the shortest education. Indicators of dampness and poor ventilation were also more common in homes of those with the shortest education. The results show that the educational level has an influence on risk factors for development of atopic disease in childhood and indicates a need of deeper understanding of life style in different socioeconomic groups. The data also indicate that various possible confounding factors need to be thoroughly investigated when analysing studies of risk factors for allergic disease in childhood.

Clinical features of atopic dermatitis at two years of age: a prospective, population-based case-control study.

While atopic dermatitis (AD) usually presents early in life, few prospective studies focus on young children with AD. The objective of this study was to characterize, phenotypically and prospectively, young children with AD. From a community birth cohort of 2,256 children, consecutive children with AD (n = 221) were followed to 2 years of age, when they were re-examined and screened for atopic sensitization (skin-prick test to foods; Phadiatop). Ninety-nine controls were also examined. AD debuted during the first year in 88% of cases. At the 2-year examination, when the children had already undergone topical treatment, 157/221 (71%) had ongoing eczema ranging among mild (45%), moderate (53%) and severe (2%). Airway problems indicating asthma had occurred in 9% of cases and 6% of controls (not significant), and allergic rhinoconjunctivitis in 5% and 0%, respectively (p<0.05). The skin-prick test to common food allergens was positive in 27% of cases and Phadiatop was positive in 15%. In 67% both tests were negative. Eczema severity did not differ between sensitized and non-sensitized children. Positive Phadiatop was more common in boys than in girls with ongoing AD (22% vs 3%, p<0.01), and more boys than girls had ongoing AD (82% vs 59%, p<0.001); otherwise, no differences attributable to gender were found.

Influence of early and current environmental exposure factors on sensitization and outcome of asthma in pre-school children.

BACKGROUND: Exposure to furred pets in early life has been considered to increase the risk of allergic sensitization and consequent development of asthma later in children. However, recently, it has been suggested that early exposure to pets prevents sensitization. The aim of this study was to evaluate the importance of early exposure to pets and other environmental risk factors in asthmatic children. METHODS: This is a follow-up study after 2 years of a previously investigated group of 193 asthmatic children, aged 1-4 years. The study was completed by 181 children, who were clinically examined; serum IgE antibodies were also measured and a questionnaire was answered. RESULTS: Children with reported exposure to cats during the first 2 years of life were more likely to have developed sensitization to cat by 4 years of age than unexposed children. High levels of cat allergen (Fel d 1> or =8 microg/g dust) were associated with an increased risk of sensitization to cat and, in combination with tobacco smoke, also with the development of more severe asthma. CONCLUSION: In young asthmatic children, early exposure to cat and tobacco smoke increased the risk of allergic sensitization and further development of more severe asthma later in childhood.

Influence of interaction of environmental risk factors and sensitization in young asthmatic children.

BACKGROUND: The increasing prevalence of asthma and allergy in many countries demands evaluation of potential risk factors to improve the possibility of prevention. OBJECTIVE: We studied the association between exposure to cat and dog allergen and allergic sensitization in young children with asthma and interactions with potential environmental risk factors. METHODS: One hundred eighty-nine young children with asthma were evaluated. IgE antibodies to cat and dog were analyzed. Questionnaires were filled in focusing on exposure to cats and dogs, environmental tobacco smoke (ETS), and signs of home dampness as indicated by window pane condensation (WPC) during the first years of life. House dust was analyzed for content of cat (Fel d 1) and dog (Can f 1) allergen. RESULTS: There was a strong association between the degree of reported exposure to cat and dog and the concentration of the respective allergens in floor dust. A dose-response relationship was found between cat exposure, measured as either reported degree of cat exposure or cat allergen levels in dust, and sensitization both to cat and dog. No such relationship was found between exposure and sensitization to dog. WPC increased the risk for sensitization to cat (odds ratio = 2.6, 95% confidence interval 1.2-5.8), whereas ETS strongly tended to do so both to cat and dog. Interaction was found between exposure to ETS, WPC, and high levels of cat allergen (>8 microg/g dust). The presence of all 3 risk factors revealed a multiplicative interaction with a high risk of sensitization to cat (odds ratio = 42.0, 95% confidence interval 3.7-472.8). CONCLUSIONS: Keeping cats indoors may be a health hazard for infants and young children at risk for development of asthma, particularly when they live in a damp house and their parents smoke.

Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy.

BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol. RESULTS: PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.

Exhaled nitric oxide in paediatric asthma and cystic fibrosis.

Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases.

Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers.

Maintenance treatment with nebulized budesonide was studied in young children with asthma not controlled without steroids. In a blind parallel-group study for 18 weeks, 102 children, mean age 22 (5- 47) months, were randomized for treatment starting with 0.25 or 1 mg b.i.d. The patients were reviewed every 3 weeks, and if symptom control had been achieved the dose was reduced, otherwise it was kept. The clinical effect was very good with both dose regimens. The median time to 7 consecutive days without any asthma symptoms was about 1 month with both, highlighting the importance of the duration of therapy rather than the benefits of a high starting dose. In 18 of 24 children who attained the placebo stage, symptoms had reappeared at the last visit. Although an overall minimal effective maintenance dose could not be demonstrated, 47% achieved symptom control on 0.25 mg b.i.d., i.e. fulfilled criteria for further dose reduction. No significant side effects were seen. On average, 25% of the nominal dose reached the patients.

Air pollution involving nitrogen dioxide exposure and wheezing bronchitis in children.

BACKGROUND: A population-based case-control study was performed in Stockholm to assess the influence of air pollution on the occurrence of severe wheezing bronchitis in children. METHODS: The study included 197 children aged 4 months to 4 years, who were hospitalized because of breathing difficulties with wheezing, and 350 population controls. Information on potential risk factors for childhood wheezing and a residential history was obtained at home interview with parents. Outdoor nitrogen dioxide (NO2) concentrations at home addresses and day care centres from birth on were estimated from validated models, mainly using data on traffic intensity from municipal registers. RESULTS: The risk of wheezing bronchitis was related to time-weighted mean outdoor NO2 exposure in girls (P = 0.02), but not in boys. A gas stove in the home appeared to be a risk factor primarily for girls. All analyses controlled for parental asthma and maternal smoking, which were independent risk factors for wheezing bronchitis. CONCLUSIONS: The results suggest that exposure to combustion products containing NO2 may be of particular importance for the development of wheezing bronchitis in girls.

Indoor environmental risk factors in young asthmatics: a case-control study.

One hundred and ninety three children with asthma and 318 controls aged 1-4 years were evaluated for atopic heredity and exposure to possible indoor risk factors for asthma-for example exposure to furred pets, tobacco smoke, and home dampness. A subgroup of cases were classified as cat and/or dog allergic on the basis of skin prick tests. Heredity for asthma was a significant risk factor (odds ratio (OR) 3.0, confidence interval (CI) 2.1 to 4.6). Environmental tobacco smoke was associated with an excess risk for asthma (OR 1.7, CI 1.1 to 2.3) and signs of home dampness tended to increase this risk (OR 1.3, CI 0.9 to 2.0). High dose exposure to cat and/or dog resulted in an increased risk only in asthma cases sensitised to cat and/or dog (OR 2.7, CI 1.0 to 7.3). A combination of high dose exposure to cat and/or dog, environmental tobacco smoke and damp housing was associated with an OR of 8.0 (CI 1.9 to 34.1). Raised indoor humidity has been shown to reflect low air exchange, which may also lead to increased doses of inhaled aeroallergens and tobacco smoke, and contribute to the interaction between the three risk factors.

Allergen cross-reactivity between Pityrosporum orbiculare and Candida albicans.

Pityrosporum orbiculare and Candida albicans extracts were separated by SDS-PAGE, and IgE binding was detected by immunoblotting with 21 patient sera that were RAST positive to both yeasts. Cross-wise inhibition was performed of IgE binding of a serum pool containing IgE antibodies to both yeasts. The pool was mixed with serial dilutions of P. orbiculare or C. albicans extracts, and incubated with strips containing separated allergen. IgE binding was quantified by densitometric scanning and percent inhibition was calculated as well as the respective ratios between required extract concentration for 50% inhibition in heterologous compared to homologous inhibition for each component (inhibition ratio). Ten components of P. orbiculare were detected by more than 60% of the sera. IgE binding to C. albicans was weak, and only to four bands was IgE binding detected by more than 30% of the sera. The most important C. albicans allergen was a 48-kDa band, to which IgE of half of the patient sera bound. There was little inhibition of IgE binding to P. orbiculare with C. albicans. Thus, all but three components exhibited an inhibition ratio higher than 100. The inhibition ratio of the 48-kDa C. albicans compound was 50, thus indicating some degree of cross-reactivity. Significant cross-reactivity was shown by C. albicans compounds of 18, 24, 26, 34, and 38 kDa, the inhibition ratios of which were less than 10. There was some degree of cross-reactivity between apparent protein allergens of the two yeasts, but IgE antibodies to C. albicans do not merely reflect sensitization to P. orbiculare.

Occurrence and clinical features of sensitization to Pityrosporum orbiculare and other allergens in children with atopic dermatitis.

One hundred and nineteen consecutive cases of children with atopic dermatitis aged 4-16 years (73 girls) from a pediatric dermatology outpatient clinic were included in a study of atopic sensitization. Structured interviews and clinical investigations were performed. IgE antibodies to common inhalant allergens, Pityrosporum orbiculare, Candida albicans, Tricophyton rubrum and Staphylococcus aureus were detected. Specific IgE antibodies frequently occurred to pollens, animal epithelia, C. albicans, house dust mites and moulds, whereas specific IgE antibodies to potential skin allergens were less prevalent. Twenty-six children (21.8%) had IgE antibodies to P. orbiculare, 14 (11.8%) to T. rubrum and 3 (2.5%) to S. aureus. Atopic dermatitis in children with one or several RAST positivities was worse, with a more chronic course, higher total eczema score, more frequent distribution in the head-neck-face regions and more itch compared to the children without serum detectable IgE antibodies. Severe itch disturbing nightly sleep was the only clinical feature that characterised P. orbiculare-positive cases. Allergy to P. orbiculare appears to be of little importance in early childhood atopic dermatitis but is likely to carry a poor prognosis.

Ventilation in homes infested by house-dust mites.

Thirty single-family homes with either high (> or = 2000 ng/g) or low (< or = 1000 ng/g) house-dust mite (HDM) allergen levels in mattress dust were examined for ventilation, thermal climate, and air quality (formaldehyde and total volatile organic compounds (TVOC). Elevated concentrations of HDM allergen in mattress and floor dust were associated with the difference in absolute humidity between indoor and outdoor air, as well as with low air-change rates of the home, particularly the bedroom. No correlation was found between concentration of TVOC or formaldehyde in bedroom air and HDM allergen concentration. In regions with a cold winter climate, the air-change rate of the home and the infiltration of outdoor air into the bedroom appear to be important for the infestation of HDM.

Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome.

The exact origin of nitric oxide (NO) in exhaled air is not known. We wanted to further investigate at what site exhaled NO is produced and to determine whether children with Kartagener's syndrome exhibited altered levels of exhaled NO. NO was measured by chemiluminescence technique in air sampled directly from the nose and in normally exhaled air of four children (2.5-13 years old) with Kartagener's syndrome, 20 healthy children, four healthy adults, and four conscious tracheostomized adults. NO was almost absent (98% reduced) in air sampled directly from the nose in four children with Kartagener's syndrome (4 +/- 1 parts per billion (ppb)), compared to age-matched controls (221 +/- 14 (ppb)). Tracheostomized adult subjects had considerably higher NO values in nasally (22 +/- 3 ppb) and orally (14 +/- 2 ppb) exhaled air, compared to levels in air exhaled through the tracheostomy (2 +/- 0 ppb). Treatment with intranasal corticosteroids for 14 days, or with antibiotics for 1 week, did not affect exhaled NO. These results clearly show that, basically, all NO in exhaled air of healthy subjects originates from the upper respiratory tract, with only a minor contribution from the lower airways. Furthermore, the absence of nasal NO in children with Kartagener's syndrome could be of use as a simple noninvasive diagnostic test.

Mite allergens during 18 months of intervention.

In Stockholm, Sweden, 17 children with newly diagnosed sensitization to house-dust mites (HDM) and 11 children with previously diagnosed HDM-sensitization were included in a study of HDM-allergen avoidance. Mattress dust was collected on repeated occasions during 18 months and assayed for concentration of major HDM allergens. During the first 12 months, the parents of the intervention group were instructed to intensify cleaning and airing of the child's bedroom. During the last 6 months of the study, the mattresses and pillows of seven children in the intervention group and sibling controls were encased in semipermeable polyurethane covers. The homes exhibited a high absolute indoor humidity throughout the year, and even during the winter the mean levels exceeded 7 g/kg. No mite allergen reduction was seen in the intervention group during the first year. However, among the newly diagnosed HDM-sensitized children, there was a mean reduction of the mattress mite allergen concentration of 83% (P = 0.02), and this was most pronounced in the homes with low humidity. At the end of the mattress encasement period, an average difference of 98% (P < 0.001) was found between the vacuumed amount of mite allergen on top of the covers and that underneath.