Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR).
To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK.
FEV1 and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes.
Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV1 (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10-8, cat p = 3.93 × 10-10, dog p = 3.03 × 10-15, grass p = 2.95 × 10-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control).
In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.
IgE; atopy; quantitative assay; lung function; airway hyperresponsiveness
Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma.
The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed.
The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r2=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively).
Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.
AMP; atopic asthma; bronchial hyper-responsiveness; methacholine
Background: Exhaled nitric oxide (eNO), which has been proposed as a measure of airway inflammation, is increased in atopic subjects. This raises the question of whether eNO provides any additional information about airway inflammation in asthmatic subjects, other than as a marker for atopy. A study was undertaken to determine whether eNO levels in a population of atopic children are associated with sensitisation or natural exposure to specific allergens, and to examine the relationship between eNO, airway responsiveness, and current respiratory symptoms.
Methods: Exhaled NO and airway responsiveness to histamine were measured in winter and in summer in 235 children aged 8–14 years who had been classified as atopic by skin prick testing. Current respiratory symptoms, defined as wheeze or cough during the month preceding the test, were measured by a parent completed questionnaire. Airway hyperresponsiveness (AHR) was defined as a dose response ratio (DRR) of >8.1 (% fall in forced expiratory volume in 1 second (FEV1)/µmol + 3).
Results: Sensitisation to house dust mite was associated with raised eNO levels in winter while sensitisation to Cladosporium was associated with raised eNO levels in both winter and summer. Grass pollen sensitisation was not associated with raised eNO levels in either season. Exhaled NO correlated significantly with DRR histamine (r=0.43, p<0.001) independently of whether the children had current symptoms or not. In children with current wheeze, those with AHR had eNO levels 1.53 (95% CI 1.41 to 1.66) times higher than those without AHR (p=0.006). Neither DRR (p=1.0) nor eNO levels (p=0.92) differed significantly between children with or without persistent dry cough in the absence of wheeze.
Conclusions: In atopic children, raised eNO levels are associated with sensitisation to perennial allergens, but not to seasonal allergens such as grass pollen. In this population, an increase in eNO is associated with AHR and current wheezing, suggesting that eNO is more than just a marker for atopy.
The relationship between sensitisation to helminths and atopy, bronchial-hyperresponsiveness and allergic diseases may differ depending on many factors, including the genes of the population studied. We sought to examine this relationship in an African cohort.
Urban Xhosa children were tested for ascaris IgE levels, bronchial hyper-responsiveness (BHR) by methacholine challenge, atopic sensitisation (skin tests to aeroallergens) and allergic disease (asthma, eczema and rhinitis) assessed by questionnaire.
Ascaris sensitisation was strongly associated with BHR but not with asthma, eczema or rhinitis. There was a dose-response relationship between increasing class of ascaris IgE and increased BHR (Prevalence ratio (PR) 1.75; CI 1.09-2.82). Higher levels of ascaris IgE were seen in those with BHR. Ascaris IgE was associated with atopic sensitisation to aeroallergens. There was a dose-response relationship between increasing class of ascaris IgE and sensitisation to one or more allergen (PR 1.65; CI, 1.27-2.13), sensitisation to house dust mites (HDM) (PR 1.79; CI, 1.29-2.46) and grass (PR 2.66; CI, 1.24-5.71) and number of positive skin prick tests (PR 1.78; CI, 1.27-2.49). Presence of any sensitisation to ascaris was associated with more than doubling the prevalence of HDM sensitisation (41.5 vs 18.5%) and almost quadrupling the prevalence of grass sensitisation (10.8 vs 2.8%).
Ascaris sensitisation was strongly associated with BHR and with atopy, but not with allergic diseases. Possible explanations might be that the type of ascaris infection that causes high levels of ascaris IgE in this genetic population may also favour the development of atopy or that atopics in Africa have upregulation of their defence system against parasitic infection. These hypotheses are not mutually exclusive.
BACKGROUND: Children who suffer from recurrent wheezy episodes are often promptly classified as asthmatic. The aim of this study was to evaluate a population of mild wheezy children with repeatedly normal spirometric tests at rest for atopy, bronchial hyperresponsiveness, and peak expiratory flow variability. METHODS: Thirty nine children aged 6-16 years with 1-12 wheezy attacks during the previous year were recruited from a community paediatric primary health care clinic serving an urban Israeli population. The conditions for inclusion were a physician-diagnosed wheeze on auscultation and normal spirometric tests at rest on at least three occasions. Evaluation included skin prick tests for atopy and a physician-completed questionnaire. In addition, two tests of bronchial hyperresponsiveness (BHR) were performed--namely, exercise-induced bronchospasm and inhaled methacholine hyperresponsiveness--as well as diurnal variability of peak expiratory flow (PV). RESULTS: One or more tests of BHR/PV were positive in 27 (69%) but repeatedly negative in 12 (31%). In terms of frequency of wheezing attacks, atopy, and questionnaire responses, there were no differences between BHR/PV and non-BHR/PV children, with the exception of a history of chest radiography proven pneumonia (only noted in the BHR/PV group). Overall, evidence of atopy (mainly indoor allergens) was noted in 21 (56%) of those tested and parental smoking in 29 (74%) of households. Thirty-two (82%) of the children complained of an exercise-related wheeze, yet exercise-induced bronchospasm was only demonstrated in nine (23%). CONCLUSIONS: This selected group of wheezy children appears to be intermediate between a normal and clearly asthmatic population and, despite the recurrent wheezy attacks, some should probably not be classified as asthmatic by conventional criteria. Important aetiological factors in the symptomatology of these children may include parental smoking and atopy as well as other elements such as viral infections.
BACKGROUND—A study was
undertaken to investigate the effect of gas cooking on the lung
function of adolescents while considering serum IgE level as a possible
sectional study was performed in 702 subjects aged 11-13 years from
primary and secondary schools in Civitavecchia and Viterbo ( Latium
region in Central Italy), categorised according to how often they were
in the kitchen while the mother cooked (never, sometimes, often). Data
were collected by questionnaire and lung function was measured by
spirometric tests. Bronchial hyperresponsiveness was evaluated by the
methacholine test, atopic status by a skin prick test, and a blood
sample was collected to determine serum IgE levels. The results were
analysed separately for boys and girls. Multiple regression analysis
was performed, taking functional parameters (FEV1,
FEV1/FVC, FEF25-75, FEF50,
FEF75) as the dependent variables and age, height, parental smoking, and father's education as independent variables.
RESULTS—There was no
association between time spent in the kitchen and lung function level
in boys, but a reduction in lung function was detected in girls which
was statistically significant for FEF75 (sometimes
-10.3%, often -11.1%). After stratifying boys and girls into four
groups on the basis of the IgE serum level (below and above the median
value of IgE), the reduction in lung function was significant in girls
with a high IgE value whereas no significant deleterious effects were
evident in girls with a low IgE value or in boys with either a low or
high IgE. The results remained substantially unchanged after excluding
girls with a response to methacholine below the concentration of
4 mg/ml, asthmatic patients, and those with positive skin prick tests.
has a harmful effect on the lung function of girls with a high serum
level of IgE. We do not know whether serum IgE, a marker of allergic
susceptibility, is a simple indicator that an inflammatory process is
in progress or whether it is involved in the pathogenesis of injury
leading to bronchial obstruction.
Bronchial hyperresponsiveness (BHR) is a common feature of asthma. However, BHR is also present in asymptomatic individuals and its clinical and prognostic significance is unclear. We hypothesised that BHR might play a role in the development of chronic obstructive pulmonary disease (COPD) as well as asthma.
In 1991 respiratory symptoms and BHR to methacholine were evaluated in 7126 of the 9651 participants in the SAPALDIA cohort study. Eleven years later 5825 of these participants were re‐evaluated, of whom 4852 performed spirometric tests. COPD was defined as an FEV1/FVC ratio of <0.70.
In 1991 17% of participants had BHR, of whom 51% were asymptomatic. Eleven years later the prevalence of asthma, wheeze, and shortness of breath in formerly asymptomatic subjects with or without BHR was, respectively, 5.7% v 2.0%, 8.3% v 3.4%, and 19.1% v 11.9% (all p<0.001). Similar differences were observed for chronic cough (5.9% v 2.3%; p = 0.002) and COPD (37.9% v 14.3%; p<0.001). BHR conferred an adjusted odds ratio (OR) of 2.9 (95% CI 1.8 to 4.5) for wheezing at follow up among asymptomatic participants. The adjusted OR for COPD was 4.5 (95% CI 3.3 to 6.0). Silent BHR was associated with a significantly accelerated decline in FEV1 by 12 (5–18), 11 (5–16), and 4 (2–8) ml/year in current smokers, former smokers and never smokers, respectively, at SAPALDIA 2.
BHR is a risk factor for an accelerated decline in FEV1 and the development of asthma and COPD, irrespective of atopic status. Current smokers with BHR have a particularly high loss of FEV1.
bronchial hyperresponsiveness; asthma; chronic obstructive pulmonary disease; smoking; epidemiological study
The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness
(BHR) that characterize asthma is achieved by the regulated accumulation and activation of
different leukocyte subsets in the lung. The development and maintenance of these processes
correlate with the coordinated production of chemokines. Here, we have assessed the role that
different chemokines play in lung allergic inflammation and BHR by blocking their activities
in vivo. Our results show that blockage of each one of these chemokines reduces both lung
leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the
eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES
(regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor
antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1α, reduces only slightly lung eosinophilia and BHR.
Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates
with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators.
These results suggest that different chemokines activate different cellular and molecular pathways
that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their
individual blockage results in intervention at different levels of these processes.
chemokines; allergic inflammation; bronchial hyperresponsiveness; eosinophilia; leukocytes
A cohort of 67 babies at risk of developing atopic disorders was followed up prospectively for 11 years. Clinical assessment and skin prick allergen sensitivity testing were performed annually over the first five years. At 11 years the cohort was restudied, symptoms were assessed by questionnaire, and bronchial reactivity (BHR) to histamine was measured. On the basis of skin testing, 35 children were atopic and 32 remained non-atopic. The expression of atopy increased with age. The lifetime prevalence of eczema, wheeze, and hay fever were 46%, 63%, and 56% respectively. The yearly period prevalence of hay fever increased with age, that of eczema declined, while that for wheeze showed a bimodal distribution with a peak before the age of 2 years and a gradual increase thereafter. Of the 21 children who wheezed before their second birthday, most never wheezed again and did not show BHR at 11 years. Of the 21 children whose first wheezing was after 2 years of age, 17 were still wheezing at 11 years and 12 showed BHR. Of the children who wheezed before 2 years of age, 10 were or became atopic, compared with 20 of the 23 children who wheezed at 11 years. These findings suggest that childhood asthma is a heterogeneous condition with atopy being strongly associated with the persistence of wheeze.
Exhaled nitric oxide (eNO) has been proposed as a noninvasive marker of airway inflammation in asthma. In asthmatic patients, exhaled NO levels have been shown to relate with other markers of eosinophilic recruitment, which are detected in blood, sputum, bronchoalveolar lavage fluid and bronchial biopsy samples. The purpose of this study was to assess the possible relationship between eNO and allergic inflammation or sensitization in childhood asthma and allergic rhinitis. Subjects consisted of 118 asthmatic children, 79 patients with allergic rhinitis, and 74 controls. Their age ranged from 6 to 15 yr old. eNO level, peripheral blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE level and specific IgE levels were measured. Methacholine challenge test and allergic skin prick test for common allergens were performed in all subjects. Atopic group (n = 206, 44.48 ± 30.45 ppb) had higher eNO values than non-atopic group (n = 65, 20.54 ± 16.57 ppb, P < 0.001). eNO level was significantly higher in patients with asthma (42.84 ± 31.92 ppb) and in those with allergic rhinitis (43.59 ± 29.84 ppb) than in healthy controls (27.01 ± 21.34 ppb, P < 0.001) but there was no difference between asthma and allergic rhinitis group. eNO also had significant positive correlations with Dermatophagoides pteronyssinus IgE level (r = 0.348, P < 0.001), Dermatophagoides farinae IgE level (r = 0.376, P < 0.001), and the number of positive allergens in skin prick test (r = 0.329, P = 0.001). eNO had significant positive correlations with peripheral blood eosinophil count (r = 0.356, P < 0.001), serum total IgE level (r = 0.221, P < 0.001), and ECP (r = 0.436, P < 0.001). This study reveals that eNO level is associated with allergic inflammation and the degree of allergic sensitization.
Exhaled Nitric Oxide; Asthma; Allergic Rhinitis; Allergy; Sensitization
Asthmatic inflammation is responsible for vital features of the disease, including bronchial hyperresponsiveness (BHR). At present we do not have precise markers for monitoring asthmatic inflammation. C-reactive protein (CRP), a marker of systemic inflammation, seemed to be a factor which could also reflect the level of asthmatic inflammation expressed by BHR. Therefore the relationship between CRP concentration and BHR was evaluated.
Materials and Methods:
One hundred and two patients entered the study. A skin prick test with a broad spectrum of common aeroallergens as well as baseline spirometry and a histamine bronchoprovocation test were performed in each subject. Blood samples for high-sensitivity CRP (hsCRP) measurement were taken before the bronchial challenge tests.
Serum hsCRP concentrations ranged from 0.20 to 14.5 mg/l (median: 1.2 mg/l, 25–75% quartiles: 0.6–2.4). Positive skin prick tests were found in 26 subjects. Bronchial hyperresponsiveness was confirmed in 42 patients (first subgroup), while 60 subjects did not demonstrate BHR (second subgroup). Among the patients with BHR, asthma was diagnosed in 33 cases and Corrao syndrome in 9. In both subgroups, serum hsCRP concentrations had similar levels (median: 1.4 mg/l, 25–75% quartiles: 0.8–2.4 and median: 0.9 mg/l, 25–75% quartiles: 0.5–2.8, respectively; p=0.297). There was no statistically significant correlation (r= −0.163, p=0.302) between serum hsCRP concentration and the level of BHR expressed as the 20% provocative concentration for histamine. In addition, hsCRP serum concentration, after adjustment for age, atopy, body mass index, and gender, was not a significant predictor of positive histamine bronchoprovocation test results (p=0.22, OR=0.86, 95% CI).
Serum hsCRP concentration is not a good marker of BHR, which is mainly dependent on asthmatic inflammation and is measured during bronchial challenge with histamine. This finding is important for interpreting and discussing results obtained from epidemiological and population-based studies on relationships between either CRP concentration and BHR or local and systemic inflammation.
asthmatic inflammation; asthma; Corrao syndrome; BHR; high-sensitivity CRP; systemic inflammation
OBJECTIVE--To investigate the relation between different types of heating and the prevalence of atopic diseases, skin test reactivity, and bronchial hyperresponsiveness. DESIGN--Cross sectional survey among school-children aged 9-11 years. Skin prick tests, pulmonary function tests, and bronchial challenge in the children and self completion of a written questionnaire by the children's parents. SUBJECTS--1958 children in a rural area in southern Bavaria, Germany. MAIN OUTCOME MEASURES--Prevalence of asthma, hay fever, and atopic dermatitis as determined by parents' answers to a questionnaire; the atopic status of the child assessed by skin prick tests; and bronchial responsiveness to cold air challenge in the children. RESULTS--After possible confounders were controlled for, the risk of developing hay fever (odds ratio = 0.57; 95% confidence interval 0.34 to 0.98), atopy defined as at least one positive reaction to a panel of common aeroallergens (0.67; 0.49 to 0.93), sensitisation to pollen (0.60; 0.41 to 0.87), and of bronchial hyperresponsiveness (0.55; 0.34-0.90) was significantly lower in children living in homes where coal or wood was used for heating than in children living in homes with other heating systems. CONCLUSIONS--Factors directly or indirectly related to the heating system used in rural Bavarian homes decrease the susceptibility of children to becoming atopic and to developing bronchial hyperresponsiveness.
The prevalence of bronchial hyperresponsiveness (BHR) to methacholine inhalation in a consecutive series of 21 patients with primary Sjögren's syndrome was studied prospectively. Slight to severe BHR was seen in 12/20 (60%) of the patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing, or intermittent breathlessness. Bronchial hyperresponsiveness was more common in patients with extraglandular symptoms (10/14, 71%) than in those with only glandular symptoms (29%). Spirometrically 29% (6/21) of the patients had 'small airways' disease', and all those had BHR. Of 6/21 (29%) who had diffuse interstitial lung disease, two had BHR. Three of the four patients with obstructive lung function were challenged with methacholine and two of them had BHR. Only two patients with BHR had normal spirometry findings. The data showed that respiratory disease--mostly mild or moderate but even severe bronchial hyperresponsiveness--is commonly seen in patients with primary Sjögren's syndrome.
Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, we discuss the relationship between atopy and BHR in the general population, asthmatic subjects, and those with allergic rhinitis. This should widen our understanding of the pathophysiology of atopy and BHR.
Allergic rhinitis; asthma; atopy; bronchial hyperresponsiveness; patients; population
5 (IL-5) has an important role in mobilisation of eosinophils from the
bone marrow and in their subsequent terminal differentiation. A study
was undertaken to determine whether inhaled and intravenous IL-5 could
induce pulmonary eosinophilia and bronchial hyperresponsiveness (BHR)
independently of these effects.
asthmatics received inhaled (15 µg) or intravenous (2 µg) IL-5 or
placebo in random order in a double blind, crossover study. Blood
samples were taken before and at 0.5, 1, 2, 3, 4,5, 24, and 72 hours
following IL-5 or placebo, and bronchial responsiveness (PC20 methacholine) and eosinophil counts in induced sputum
levels were markedly increased 30 minutes after intravenous IL-5
(p=0.002), and sputum IL-5 levels increased 4and 24 hours after
inhaled IL-5 (p<0.05). Serum eotaxin was raised 24 hours after
intravenous IL-5 but not after inhaled IL-5 or placebo. Blood
eosinophils were markedly reduced 0.5-2 hours after intravenous IL-5
(p<0.05), followed by an increase at 3, 4, 5,and 72 hours (p<0.05).
Sputum eosinophils rose significantly in all three groups at 24 hours
but there were no differences between the groups. Bronchial
responsiveness was not affected by IL-5.
of IL-5 appear to be mainly in the circulation, inducing peripheral
mobilisation of eosinophils to the circulation without any effect on
eosinophil mobilisation in the lungs or on bronchial responsiveness.
Wheezing during infancy has been linked to early loss of pulmonary function. We prospectively investigated the relation between bronchial hyperresponsiveness (BHR) and progressive impairment of pulmonary function in a cohort of asthmatic infants followed until age 9 years. We studied 129 infants who had had at least three episodes of wheezing. Physical examinations, baseline lung function tests and methacholine challenge tests were scheduled at ages 16 months and 5, 7 and 9 years. Eighty-three children completed follow-up. Twenty-four (29%) infants had wheezing that persisted at 9 years of age. Clinical outcome at age 9 years was significantly predicted by symptoms at 5 years of age and by parental atopy. Specific airway resistance (sRaw) was altered in persistent wheezers as early as 5 years of age, and did not change thereafter. Ninety-five per cent of the children still responded to methacholine at the end of follow-up. The degree of BHR at 9 years was significantly related to current clinical status, baseline lung function, and parental atopy. BHR at 16 months and 5 years of age did not predict persistent wheezing between 5 and 9 years of age, or the final degree of BHR, but it did predict altered lung function. Wheezing that persists from infancy to 9 years of age is associated with BHR and to impaired lung function. BHR itself is predictive of impaired lung function in children, strongly pointing to early airway remodeling in infantile asthma.
The prevalence of bronchial hyperresponsiveness in adult populations is not known. To document its prevalence and distribution and to determine the factors associated with it, a random sample of the adult population of Busselton, Western Australia, was studied. Spirometric function, bronchial responsiveness to histamine, and atopic responses to skin prick tests were measured. Respiratory symptoms were determined by questionnaire. Data were obtained from 916 subjects. Of these, 876 underwent a histamine inhalation test and bronchial hyperresponsiveness to histamine (defined as a dose of histamine provoking a 20% fall in FEV1 equal to or less than 3.9 mumol) was found in 10.5%. Another 40 subjects with poor lung function were tested with a bronchodilator and 12 were found to have bronchial hyperresponsiveness (defined as a greater than 15% increase in FEV1), making the total prevalence of bronchial hyperresponsiveness 11.4%. The prevalence of current asthma, defined as bronchial hyperresponsiveness plus symptoms consistent with asthma in the last 12 months, was 5.9%. The distribution of bronchial hyperresponsiveness in the studied population was continuous. There was a significant association between it and respiratory symptoms, atopy, smoking, and abnormal lung function (p less than 0.001 for all associations). There was no association with age, sex, or recent respiratory tract infection.
hyperresponsiveness and airway inflammation are distinctive features of
asthma. Evaluation of nitric oxide (NO) levels in expired air have been
proposed as a reliable method for assessing the airway inflammatory
events in asthmatic subjects. A study was undertaken to evaluate
whether airway hyperresponsiveness is related to levels of exhaled NO.
steroid-naive atopic children with mild intermittent asthma of mean
(SD) age 11.8 (2.3) years and 28 age matched healthy controls were
studied to investigate whether baseline lung function or airway
hyperresponsiveness is related to levels of exhaled NO. Airway
responsiveness was assessed as the dose of methacholine causing a 20%
decrease in forced expiratory volume in one second (FEV1)
from control (PD20 methacholine) and exhaled NO levels were
measured by chemiluminescence analysis of exhaled air.
asthmatic children had significantly higher NO levels than controls
(mean difference 25.87 ppb (95% CI 18.91 to 32.83); p<0.0001) but
there were no significant differences in lung function parameters
(forced vital capacity (FVC), FEV1 (%pred), and forced
expiratory flows at 25-75% of vital capacity (FEF25-75%)). In the asthmatic group exhaled NO levels were not significantly correlated with baseline lung function values or
results suggest that levels of exhaled NO are not accurate predictors
of the degree of airway responsiveness to inhaled methacholine in
children with mild intermittent asthma.
Sputum eosinophilia is observed frequently in patients with rhinitis. Sputum eosinophilia in patients with non-asthmatic allergic rhinitis has been suggested to be related to nonspecific airway hyperresponsiveness (AHR). However, the clinical significance of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR has not been determined. We conducted a retrospective study examining the influence of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR on pulmonary function and expression of fibrosis-related mediators.
Eighty-nine patients with moderate-to-severe perennial rhinitis without AHR were included. All underwent lung function tests (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), skin tests to inhalant allergens, methacholine bronchial challenge tests, and hypertonic saline-induced sputum to determine eosinophil counts. Sputum mRNA levels for transforming growth factor-β (TGF-β), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also examined. Patients were divided into two groups according to the presence of sputum eosinophilia (≥3%, eosinophilia-positive [EP] and <3%, eosinophilia-negative [EN] groups).
FEV1 was significantly lower (P=0.04) and FEV1/FVC tended to be lower (P=0.1) in the EP group than in the EN group. In sputum analyses, the MMP-9 mRNA level (P=0.005) and the ratio of MMP-9 to TIMP-1 expression (P=0.01) were significantly higher in the EP group than in the EN group. There was no significant difference in TGF-β mRNA expression between the two groups.
Sputum eosinophilia in patients with moderate-to-severe perennial rhinitis without AHR influenced FEV1 and the expression pattern of fibrosis-related mediators.
Sputum; eosinophil; rhinitis; forced expiratory volume; matrix metalloproteinase-9
Background: Pulmonary complications are a major cause of morbidity and mortality in sickle cell disease (SCD). The relationship of asthma with SCD and acute chest syndrome (ACS) remains uncertain. A study was undertaken to test the hypotheses that asthma and bronchial hyperreactivity (BHR) are more common in children with SCD than in ethnic matched controls and that SCD children with atopic asthma are more likely to have recurrent episodes of ACS.
Methods: A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was administered and skin prick tests undertaken in 80 children with SCD and 80 ethnic matched controls aged 5–10 years. BHR was assessed by measurement of forced expiratory volume in 1 second before and after a bronchodilator (albuterol 200 µg) or an exercise challenge.
Results: Asthma (48% v 22%, p = 0.002) and BHR (p = 0.02) but not atopy were more common in children with SCD than in controls. Atopy (66.6% v 29%, p = 0.007) and asthma (80% v 40%, p = 0.005), particularly atopic asthma (53% v 12%, p<0.001), were more common in children with SCD who had suffered recurrent episodes of ACS than in those who had suffered a single or no episode.
Conclusions: Asthma and BHR are more common in children with SCD than in ethnic matched controls, and atopic asthma appears to be associated with recurrent ACS. Early and effective anti-asthma therapy might reduce the pulmonary morbidity associated with SCD.
Background: C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of adverse cardiovascular events. Respiratory impairment is also associated with cardiovascular risk. Although some studies have found an inverse relationship between lung function and markers of systemic inflammation, only one study has reported a relationship between lung function and CRP levels. In contrast, little is known about the relationship between bronchial hyperresponsiveness (BHR) and systemic inflammation. The association between lung function and CRP and between BHR and CRP has been investigated.
Methods: As part of the European Community Respiratory Health Survey follow up study serum CRP levels, forced expiratory volume in 1 second (FEV1), and BHR to methacholine (⩾20% decrease in FEV1 to <4 mg methacholine) were measured in 259 adults aged 28–56 years free of cardiovascular disease or respiratory infection.
Results: Mean (SD) FEV1 (adjusted for age, sex, height, and smoking status) was lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50 (0.44) l/s; p<0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in subjects with lower CRP levels (low+middle tertiles). Similar results were obtained when the potential confounding factors were taken into account. Similar patterns of results were found in non-smokers and in non-asthmatic subjects.
Conclusions: Increased CRP levels are strongly and independently associated with respiratory impairment and more frequent BHR. These results suggest that both respiratory impairment and BHR are associated with a systemic inflammatory process.
For individual exposures, effect modification by atopy or smoking has been reported on the occurrence of occupational airway disease. It is unclear if effect modification can be studied in a general population by an aggregated exposure measure. Assess relationship between airway obstruction and occupational exposure using a job-exposure-matrix (JEM) classifying jobs into 3 broad types of exposure, and test for effect modification by atopy, and smoking.
Data from 1,906 subjects were analyzed, all participants of the European Community Respiratory Health Survey. Job titles were categorized by an a priori constructed job exposure matrix into three classes of exposure to respectively organic dust, mineral dust, and gases/ fumes. Relationships were assessed for 'current wheeze', bronchial hyperresponsiveness (BHR), 'current asthma' (wheeze+BHR), and 'chronic bronchitis' (morning phlegm or morning cough), and lung function.
Subjects with organic dust exposure in their work environment more frequently had 'current asthma' (OR 1.48, 95% C.I. 0.95;2.30), and a lower FEV1 (-59 mL, 95% C.I. -114;-4). The relationship was only present in asthmatic workers, and their risk was four-fold greater than in subjects with either atopy or exposure alone. Mineral dust exposure was associated with 'chronic bronchitis' (OR 2.22, 95% C.I. 1.16;4.23) and a lower FEV1/FVC ratio (-1.1%, 95% C.I. -1.8;-0.3). We observed an excess risk in smokers, greater than the separate effects of smoking or mineral dust exposure together.
Occupational exposure to organic dust is associated with an increased risk of asthma, particularly in atopics. Chronic bronchitis occurs more frequently among individuals exposed to mineral dust, and smoking doubles this risk.
Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma?
Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed.
Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy.
Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question.
Fifty children with at least one hospital admission for acute lower airway obstruction in the first 2.5 years of life were assessed at 3 years of age to determine the relationship between atopy, bronchial responsiveness, and the pattern of their symptoms. Bronchial responsiveness was measured by assessing the effect of inhaled metacholine, using the change in transcutaneous oxygen tension (PtCO2) as an indirect measure of response. Symptom patterns were defined by the number of wheezing episodes associated with colds and the presence or absence of cough or wheeze unrelated to viral infections. Forty per cent of the children were found to be atopic by skin prick test or history. In contrast to the situation found in older children and adults, the non-atopic children had significantly greater bronchial responsiveness (lower mean concentration of methacholine causing a 20% fall in PtCO2, the PC20) than the atopic children and significantly more of them had an onset of respiratory symptoms in the first year of life. Cough and wheeze in the absence of colds was more frequently found in the atopic children as was the use of continuous medication. However, the number of reported acute episodes of wheeze associated with colds was the same in the two groups. The findings of the study suggest that in this hospital based group of children, acute wheeze associated with colds in the first three years of life is independent of the finding of atopy and that bronchial responsiveness in this age group may have a different pathogenesis from that in older subjects.
BACKGROUND--It is not clear whether asymptomatic bronchial hyperresponsiveness (BHR) in children is a risk factor for the subsequent development of asthma. A longitudinal study was conducted to determine the predictive value of BHR for the development of asthma in a primary care patient population. METHODS--A standard free running asthma screening test (FRAST) was applied to 956 schoolchildren aged between 4 and 11 years in 1985. Peak expiratory flow (PEF) rates were measured before hard running for six minutes and following a three minute rest period. Children with a fall in PEF of more than 15% were labelled as having a positive FRAST. Clinical data from the patients' notes and from symptom questionnaires were compared with age and sex matched controls for children known to have asthma, and for those with a positive FRAST but no asthma (BHR group). Over the ensuing six years to 1991 further clinical data were gathered to compare the development of asthma and other diseases of the airways in both the BHR groups and their controls. RESULTS--Of the 956 children exercised in 1985, 60 who were not known to have asthma had an abnormal test. Of the 55 of these studied in 1991, 32 (58%) had developed asthma. The sensitivity of a positive FRAST for the development of asthma was 58%, its specificity 97%, and positive predictive value 72%. Hay fever, eczema, otitis media, "bronchitis," and family history of atopy also occurred more commonly in this group. CONCLUSIONS--Asymptomatic BHR, as shown by exercise challenge, can predict the development of clinical asthma. This study has also shown a relation between BHR, asthma, and other diseases of the airways, notably upper respiratory tract infection, "bronchitis," and otitis media.