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Biomedical subjects

A L James

Publications and source records attributed to A L James.

At least 19 recordsLinked to original sources

Do bronchial biopsies represent mast cell density in airways? A stereological study.

Endobronchial biopsy specimens may not adequately represent inflammatory cell counts throughout the airway wall. The present study aimed to compare mast cell density in biopsies and airway sections using both stereological and nonstereological methods. Post mortem biopsies and adjacent transverse sections were obtained from a mean of five proximal airways per case in 10 subjects who had died of nonrespiratory causes. Tryptase-positive mast cells were measured stereologically in 30-mum sections and nonstereologically in 5-microm sections using an optical disector (cells x mm(-3)) and cell profiles (cells x mm(-2)), respectively. Reference areas included the inner and total airway wall and to 100 microm below the basement membrane. Case means, based on four or more biopsy sites, significantly correlated with those on transverse sections for counts over the inner airway wall only, using both stereological and nonstereological methods. Cells x mm(-3) and cells x mm(-2) were significantly correlated within all reference areas. When endobronchial biopsies are obtained from at least four proximal airways per case, inter-subject comparisons of mean mast cell density in the inner airway wall are as well represented by counts on biopsies as they are on transverse sections. This is the case using either three-dimensional, stereological or two-dimensional, nonstereological methods.

Adolescent↗

AluyMICB dimorphism within the class I region of the major histocompatibility complex is associated with asthma and airflow obstruction in the Busselton population.

AIM: To examine the association between the Alu dimorphism within the first intron of the MICB gene and asthma and airflow obstruction. Background The highly polymorphic non-classical MHC class I polypeptide-related (MIC) genes, MICA and MICB, encode stress inducible glycoproteins, which are expressed on a variety of epithelial cells, including those of the lungs. METHODS: AluyMICB genotyping was performed on 1109 subjects from the Busselton Health Study. From a standard questionnaire, 359 individuals indicated that they had been diagnosed by a doctor with asthma. Lung function was assessed by the forced expired volume in 1 second (FEV1) and expressed as a percent of the predicted value. Airflow obstruction was defined as FEV1<80% predicted. RESULTS: In men, a dominant relationship was found between the AluyMICB DD genotype and asthma (P=0.006; chi2(2)=7.65). Furthermore, multivariate analysis adjusted for age, height, weight and body mass index (BMI) showed a relationship between DD genotype and asthma in men in a dominant model (odds ratio (OR)=1.97; 95% confidence interval (CI)=1.11-3.51; P=0.021). In women, an association was found between the AluyMICB II genotype and FEV1 percent predicted as a continuous variable (P=0.001). When adjusted for age and BMI, it showed a significant relationship between AluyMICB and airflow obstruction in a dominant model (OR=14.11%, 95% CI 3.29-60.57, P<0.001). However, no association was found between the AluyMICB II genotypes and airflow obstruction in men. CONCLUSION: These findings suggest the possible involvement of a MHC class I gene in abnormal airway structure in women and airway function in men.

Adult↗

Evaluation of novel fluorogenic substrates for the detection of glycosidases in Escherichia coli and enterococci.

AIMS: Enzyme substrates based on 4-methylumbelliferone are widely used for the detection of Escherichia coli and enterococci in water, by detection of beta-glucuronidase and beta-glucosidase activity respectively. This study aimed to synthesize and evaluate novel umbelliferone-based substrates with improved sensitivity for these two enzymes. METHODS AND RESULTS: A novel beta-glucuronide derivative based on 6-chloro-4-methylumbelliferone (CMUG) was synthesized and compared with 4-methylumbelliferyl-beta-D-glucuronide (MUG) using 42 strains of E. coli in a modified membrane lauryl sulfate broth. Over 7 h of incubation, the fluorescence generated from the hydrolysis of CMUG by E. coli was over twice that from MUG, and all of the 38 glucuronidase-positive strains generated a higher fluorescence with CMUG compared with MUG. Neither substrate caused inhibition of bacterial growth in any of the tested strains. Four beta-glucosidase substrates were also synthesized and evaluated in comparison with 4-methylumbelliferyl-beta-D-glucoside (MU-GLU) using 42 strains of enterococci in glucose azide broth. The four substrates comprised beta-glucoside derivatives of umbelliferone-3-carboxylic acid and its methyl, ethyl and benzyl esters. Glucosides of the methyl, ethyl and benzyl esters of umbelliferone-3-carboxylic acid, were found to be superior to MU-GLU for the detection of enterococci, especially after 18 h of incubation, while umbelliferone-3-carboxylic acid-beta-D-glucoside was inferior. However, the variability in detectable beta-glucosidase activity among the different strains of enterococci in short-term assays using the three carboxylate esters (7 h incubation) may compromise their use for rapid detection and enumeration of these faecal indicator bacteria. CONCLUSIONS: The beta-glucuronidase substrate CMUG appears to be a more promising detection system than the various beta-glucosidase substrates tested. SIGNIFICANCE AND IMPACT OF THE STUDY: The novel substrate CMUG showed enhanced sensitivity for the detection of beta-glucuronidase-producing bacteria such as E. coli, with a clear potential for application in rapid assays for the detection of this indicator organism in natural water and other environmental samples.

Cellulases↗

Mortality and airflow obstruction in asthma: a 17-year follow-up study.

BACKGROUND: Asthma is associated with fixed airflow obstruction and an increased risk of death. The aim of this study was to relate asthma mortality and airflow obstruction to severity of asthma in a cohort of patients with chronic asthma studied over a 17-year period. METHODS: In 1980, asthma severity based on symptoms, asthma duration, treatment and smoking habits were assessed and lung function was measured after maximal therapy in 89 patients. In 1997, mortality was recorded and 44 of 60 patients known to be alive were restudied. RESULTS: Eighteen patients had died: eight deaths were associated with asthma (seven occurred before and one after 1990). The risk of death was higher with decreased forced expiratory volume in 1 s (FEV1), increased FEV1 variability, age and treatment requirements but not symptom severity, at initial study. In the patients restudied, asthma severity and FEV1 variability decreased whereas the dose of inhaled corticosteriods increased 2.8-fold. Highest FEV1 was negatively related to treatment score and smoking history at initial study, but not at follow up and was <80% predicted in 19 (43%) patients, 11 of whom had never smoked. The mean (+/-standard deviation) decrement in FEV1 was 32 +/- 24 mL/year and correlated positively with FEV1 at initial study, smoking history, age of onset of asthma and treatment requirements at follow up. CONCLUSION: In this cohort study, asthma was associated with chronic airflow obstruction and that with increased risk of mortality. Symptoms and mortality risk improved in association with increased reported use of inhaled corticosteroids; however, there was ongoing chronic airflow obstruction.

Adult↗

Endoscopic treatment of congenital H-Type and recurrent tracheoesophageal fistula with electrocautery and histoacryl glue.

OBJECTIVE: Congenital H-Type tracheoesophageal fistulae (H-Type TEF) and recurrent fistulae after primary repair of esophageal atresia represent a difficult problem in diagnosis and management. The treatment traditionally involved an open technique via a cervical or thoracic route, approaches with high morbidity and mortality rates of up to 50%. Endoscopic closure of fistulae has been reported with various techniques such as tissue adhesives, electrocautery, sclerosants and laser. However, the published case series contain a small number of patients with usually short-term follow-up. The aim of this paper is to present the experience of a decade at Toronto's Hospital for Sick Children, using diathermy and histoacryl tissue adhesive and discuss the indications and limitations of this technique. METHODS: Since 1995, 192 patients have been managed in this institution with tracheoesophageal fistulae of which 10 patients have been treated endoscopically. The fistulae were both of H-Type and recurrent tracheoesophageal fistulae following surgery for esophageal atresia and fistula division. One fistula occurred following trauma. The procedure was undertaken under general anesthesia in the image guided therapy suite under fluoroscopic control. Flexible ball electrocautery and injection of histoacryl glue were used either on their own or in combination. RESULTS: Fistula closure was achieved in 9 out of 10 fistulae. Four patients had a second endoscopic procedure. No major respiratory or other complications were encountered in association with the procedure. Follow-up has been between 3 months and 9 years. CONCLUSION: We conclude, endoscopic treatment of tracheoesophageal fistulae with electrocautery and histoacryl glue has been a safe and successful technique of managing H-Type and recurrent tracheoesophageal fistulae. In this paper, we discuss the indications and the surgical steps of the procedure. We highlight that diathermy should be carefully controlled and applied preferably in the small non-patulous fistulae. A fistula that has not closed after two endoscopic attempts is not suitable for further endoscopic treatment and therefore an external approach should be recommended.

Child↗

Adjuvant antiviral therapy for recurrent respiratory papillomatosis.

BACKGROUND: Recurrent respiratory papillomatosis is a condition characterised by benign papillomatous (wart-like) growths in the upper airway. It can affect both adults and children causing airway-obstruction and voice change. Treatment usually involves repeated surgical debulking of the papillomata, and several agents have been proposed as adjuvants to surgical debulking. These include antivirals, administered systemically or injected into the lesions. OBJECTIVES: To assess the effectiveness of antiviral agents as adjuvant therapy in the management of recurrent respiratory papillomatosis in children and adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2004), MEDLINE (January 1966 to November 2004), and EMBASE (January 1985 to November 2004) in December 2004. We checked reference lists of articles, contacted pharmaceutical companies and contacted leading experts in the field for further studies. SELECTION CRITERIA: All randomised controlled trials. DATA COLLECTION AND ANALYSIS: One hundred references were identified from the searches. Twenty-five were appropriate for retrieval and assessed for eligibility by the authors. None met the inclusion criteria. MAIN RESULTS: No controlled trials were identified. AUTHORS' CONCLUSIONS: There was insufficient evidence from controlled trials on which to base reliable conclusions about the effectiveness of antiviral agents as adjuvant therapy in the management of recurrent respiratory papillomatosis. Further research is required before any specific antiviral adjuvant therapy can be recommended.

Adult↗

Time to death, airway wall inflammation and remodelling in fatal asthma.

Fatal asthma is characterised pathologically by airway wall remodelling, eosinophil and neutrophil infiltration, accumulation of mucus in the airway lumen and smooth muscle shortening. The durations of fatal attacks of asthma show a clear bimodal distribution. Airway smooth muscle contraction and the accumulation of luminal mucus may contribute to death from asthma and relate to time to death. The current authors have examined these two components in uninflated lung tissue in cases of fatal asthma from the second Victorian asthma mortality study. Based on time from onset of symptoms to death, cases fell into two distinct groups: short course <3 (1.5+/-0.6 mean+/-sd) h; and long course >8 (12.3+/-5.9) h. Short course cases had more muscle shortening, higher levels of salbutamol and higher ratios of neutrophils to eosinophils than long course cases, who tended to have more mucus in the lumen. In conclusion, this study confirms the dichotomy of both time to death and the eosinophil/neutrophil ratio in cases of fatal asthma. It suggests that in short course cases acute airway narrowing is due, predominantly, to bronchoconstriction despite higher blood levels of salbutamol. Mucus accumulation may be more important in long course cases.

Adolescent↗

Management of bilateral choanal atresia in the neonate: an institutional review.

The endoscopic repair of bilateral choanal atresia using powered instrumentation has become a common procedure performed by many pediatric otolaryngologists. A 10-year retrospective review of the management of bilateral choanal atresia in the neonate was undertaken at the Hospital for Sick Children, a tertiary care pediatric institution in Toronto. Although many techniques were used for repair including the endoscopic technique, a simple puncture, dilation and stenting technique was used most frequently. Fifty-two patients were identified who underwent this technique. The modifications and refinements of this technique and post-operative care will be detailed. The results were as follows. All patients were successfully extubated within 24h of the operation. The average duration of nasal stenting was 3 months. Three patients required re-stenting, one of which had nasal stenting for the first year of life. This patient was born prematurely, had trisomy-21 and was stented weighing a mere 600g. One patient had a small septal perforation and only two patients required transpalatal repair later in life for persistent nasal symptoms. There were no CNS complications and no incidence of significant nasal hemorrhage or infection. All patients received topical antibiotics and steroid drops during the stenting period. Mitomycin C was not used. Granulation tissue was not a significant problem. Despite the advances in endoscopic technology, the puncture, dilation and stenting technique is still the senior author's preferred method of repair for neonatal bilateral choanal atresia.

Choanal Atresia↗

Contralateral suppression of DPOAE measured in real time.

The aim of this study was to measure contralateral suppression of distortion product otoacoustic emissions (DPOAE) in real time. A total of 10 human subjects were studied with a novel device to record DPOAE without signal time averaging, using digital narrow band pass filtering. Real time DPOAE levels were recorded at 2f1-f2 using primary tone settings of f2/f1 = 1.22 and L1 = 70 dB SPL, L2 = 65 dB SPL, at five values of f2 between 2.2 and 7.7 kHz. An acoustic stimulus was applied intermittently to the contralateral ear to cause DPOAE suppression. Characteristic features of contralateral suppression were identified and distinguished from small spontaneous variations in the real time DPOAE signal. Magnitude of suppression increased with contralateral stimulus intensity. Onset latency of suppression was around 43 ms (31-95 ms). Potential clinical applications are discussed in the light of these findings, including a role in improving the specificity of neonatal hearing screening.

Acoustic Stimulation↗

Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma.

BACKGROUND: Mucus plugging of the airways is invariably seen in cases of fatal asthma, mucus production is associated with asthma attacks, and the area of submucosal glands is increased in asthma. Mediators secreted from mast cells and neutrophils can stimulate mucous gland secretion. A study was undertaken to count the mast cells and neutrophils in submucosal glands and to relate cell numbers to the presence of mucus in the airway lumen. METHODS: Cartilaginous airways obtained at necropsy from cases of fatal asthma (n=8), non-fatal asthma (n=8), and control cases (n=8) were examined. Contiguous transverse sections were stained for mast cell tryptase and neutrophil elastase, and with Periodic Acid Schiff solution to identify mucus. Mucous gland area, lumen area, and the percentage of the relaxed lumen area occupied by mucus (mucus occupying ratio, MOR) were measured. Mast cells (intact and degranulated) and neutrophils per area of submucosal gland were calculated. RESULTS: Compared with controls, the cases of fatal asthma had increased mucous gland area, MOR, percentage of degranulated mast cells, and numbers of neutrophils in the submucosal glands (p<0.05). In cases of non-fatal asthma the MOR and the numbers of mast cells and neutrophils in the submucosal glands were increased (p<0.05). When all cases were pooled together, the MOR correlated with the total number of mast cells (r=0.55, p=0.005) and with the number of degranulated mast cells in the submucosal glands (r=0.51, p=0.013), but not with the number of neutrophils (r=0.21, p=0.121). CONCLUSION: These results show that mucous gland area, MOR, and mucous gland inflammation are increased in asthma and that degranulation of mast cells may contribute to secretion of mucus into the lumen in cases of fatal asthma.

Adult↗

Distribution and degranulation of airway mast cells in normal and asthmatic subjects.

It was hypothesized that the distribution and activation of mast cells across the airway wall may reflect their function in asthma. The density of mast cells (intact and degranulated) within airway compartments in cartilaginous and membranous airways, obtained from autopsies on patients with fatal asthma, nonfatal asthma, and nonasthmatic control cases have been examined. In cartilaginous airways, the mean+/-SE density of mast cells in control cases was 27+/-9 cells x mm(-2). It was similar in nonfatal asthma (24+/-2 cells x mm(-2)) but reduced (p<0.05) in fatal asthma cases (16+/-2 cells x mm(-2)). In membranous airways, the density of mast cells in control cases was 155+/-21 cells x mm(-2) and was higher (p<0.05) in cases of nonfatal (270+/-51 cells x mm(-2)) and fatal asthma (219+/-26 cells x mm(-2)). Mast-cell density was greatest on the smooth muscle and mucous glands in cartilaginous airways and on the smooth muscle and outer airway wall in membranous airways. The percentage of degranulated mast cells was higher (p<0.05) in cases of asthma, related to disease severity, and was higher in cartilaginous than membranous airways. Degranulation was greatest on the smooth muscle in fatal asthma cases. Mast-cell distribution and degranulation varies between cartilaginous and membranous airways and across the airway wall. Degranulation of mast cells is related to asthma severity. The increased degranulation in proximal airways may reflect stimulation via the inhaled route.

Adolescent↗

Betahistine for Menière's disease or syndrome.

BACKGROUND: Menière's disease is characterised by attacks of hearing loss, tinnitus and disabling vertigo. Betahistine is used by many people to reduce the frequency and severity of these attacks but there is conflicting evidence relating to its effects. OBJECTIVES: The objective of this review was to assess the effects of betahistine in people with Menière's disease. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (The Cochrane Library issue 4,1999), MEDLINE (January 1966 to December 1999), EMBASE (January 1985 to December 1999) and Index Medicus (1962 to 1966). We checked reference lists of articles and contacted pharmaceutical companies for further studies. SELECTION CRITERIA: Randomised controlled studies of betahistine versus placebo in Menière's disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for further information. MAIN RESULTS: Six trials involving 162 patients were included. No trial met the highest quality standard set by the review because of inadequate diagnostic criteria or methods, and none assessed the effect of betahistine on vertigo adequately. Most trials suggested a reduction of vertigo with betahistine and some suggested a reduction in tinnitus but all these effects may have been caused by bias in the methods. One trial with good methods showed no effect of betahistine on tinnitus compared with placebo in 35 patients. None of the trials showed any effect of betahistine on hearing loss. No adverse effects were found with betahistine. REVIEWER'S CONCLUSIONS: There is insufficient evidence to say whether betahistine has any effect on Menière's disease.

Betahistine↗

Gibbs sampling-based segregation analysis of asthma-associated quantitative traits in a population-based sample of nuclear families.

Asthma is a common, complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, and increased airway responsiveness are physiological traits that are characteristic of asthma. Few studies have investigated major gene effects for these traits in a population-based sample. Further, it is not known if any putative major genes may be common to two or more of these traits. We investigated the existence and nature of major genes modulating asthma-associated quantitative traits in an Australian population-based sample of 210 Caucasian nuclear families. The sharing of these major genes was also investigated. Segregation analysis was based upon a Markov Chain Monte Carlo (Gibbs sampling) approach as implemented in the program BUGS v0.6. All models included adjustment for age, height, tobacco smoke exposure, and gender. The segregation of total IgE levels, blood eosinophil counts, and dose-response slope (DRS) of methacholine challenge were all consistent with major loci at which a recessive allele acted to increase or decrease the phenotype. The respective estimated frequencies of the recessive alleles were 68% (total IgE), 10% (blood eosinophil count), and 27% (DRS). Extensive modelling suggested that the major loci controlling total serum IgE levels, blood eosinophil counts, and airway responsiveness represent different genes. These data provide evidence, for the first time, of the existence of at least 3 distinct genetic pathways involving major gene effects on physiological traits closely associated with asthma. These results have implications for gene discovery programs.

Adolescent↗

Synthesis and evaluation of novel fluorogenic substrates for the detection of bacterial beta-galactosidase.

AIMS: A widely used coumarin derivative is 7-hydroxy-4-methylcoumarin-beta-D-galactoside (4-methylumbelliferone-beta-D-galactoside; 4-MU-GAL). This galactoside is utilized as a substrate for the detection of the beta-galactosidase activity of coliform bacteria in water analysis. The intense fluorescence of coumarin-based molecules has enabled them to be incorporated into enzyme-based tests for the quantitative assay of indicator bacteria. The aim of this present study was to evaluate the potential of other coumarin derivatives, by synthesis of a selection of core coumarin molecules. METHODS AND RESULTS: Several coumarin derivatives were found to be more promising than 4-MU, with ethyl-7-hydroxycoumarin-3-carboxylate (EHC) giving a combination of greater fluorescence over a broad pH range and reduced growth inhibition with 12 representative coliform strains. On conversion to a beta-galactoside derivative, EHC-GAL generated a more rapid fluorescence than any other tested substrate. CONCLUSIONS: When tested in a broth assay format, based on most probable number (MPN), low numbers of coliforms were detected with EHC-GAL around 1 h earlier than with 4-MU-GAL. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study suggests that EHC-GAL should be evaluated as a substrate for the detection of coliforms in water analysis, due to a combination of the following favourable features: (i) reduced toxicity; (ii) increased fluorescence; (iii) pH stability of fluorescence; and (iv) rapid detection.

Bacteriological Techniques↗

Fluorogenic substrates for the detection of microbial nitroreductases.

AIMS: To synthesize and evaluate fluorogenic substrates for the detection of microbial nitroreductases. These substrates, all based on 7-nitrocoumarin, may be reduced to form fluorescent aminocoumarins. METHODS AND RESULTS: Thirty pathogenic microbial strains, including both bacteria and yeasts, were examined for nitroreductase activity in a whole-cell assay. All strains readily reduced each of the seven substrates to generate fluorescence, suggesting the widespread presence of nitroreductase activity in pathogenic bacteria. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: These novel substrates facilitate the direct detection of nitroreductase activity and have potential as sensitive indicators of microbial growth.

Bacteria↗

Tightening the net: children, community, and control.

The recent move to revitalize social democracy in the UK under the New Labour government, explored by Giddens as 'the Third Way', embraces many of Etzioni's ideas on communitarianism. The principles that emerge from these political philosophies, such as the involvement of local communities in policy consultations and implementation, have largely been welcomed as a reflection of the aim of revitalizing civic society in the context of a range of social policies. It is argued, however, that for children, contrary to this general trend, many of these policies represent attempts to increase the social control of children. Their effect has been to restrict children's agency and their rights, rather than to increase their participation as citizens, and thus,in spite of the requirements of the UN Convention on the Rights of the Child, children continue to be marginalized.

Adult↗

Familial aggregation and heritability of adult lung function: results from the Busselton Health Study.

Decreased spirometric indices are characteristic of asthma and other respiratory diseases. The aim of this study was to investigate the genetic and environmental components of variance of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured in adulthood in an Australian population-based sample of 468 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits with asthma and atopic rhinitis were also investigated. Serial cross-sectional studies were conducted in the town of Busselton in Western Australia between 1966 and 1981 and follow-up of previous attendees was undertaken in 1995. Data from each subject included in this study were from a single survey in adulthood (25-60 yrs of age) when the subject was as close to age 45 yrs as possible. Multivariate analysis suggested that FEV1 and FVC levels were associated with age, sex, height, tobacco smoke exposure, asthma and atopic rhinitis. After adjustment for relevant covariates, FEV1 levels had a narrow-sense heritability (h2N) of 38.9% (SE 9.1%). FVC levels had an h2N of 40.6% (SE 8.9%). Extended modelling demonstrated little overlap in the genetic determinants of asthma or atopic rhinitis and either FEV1 or FVC levels. The results of this study were consistent with the existence of important genetic determinants of adult lung function that are independent of asthma or other atopic disease, cigarette smoking, height, age or sex.

Adult↗

Familial aggregation and heritability of asthma-associated quantitative traits in a population-based sample of nuclear families.

Asthma is a common, genetically complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, variably reduced spirometric measures and increased airway responsiveness (AR) are physiological traits which are characteristic of asthma. We investigated the genetic and environmental components of variance of serum total and specific IgE levels, blood eosinophil counts, the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and AR in an Australian population-based sample of 232 Caucasian nuclear families. With the exception of FVC levels, all traits were closely associated with clinical asthma in this population. Loge total serum IgE levels had a narrow-sense heritability (h2N) of 47.3% (SE = 10. 0%). Specific serum IgE levels against house dust mite and Timothy grass, measured as a RAST Index, had a h2N of 33.8% (SE = 7.3%). FEV1 levels had a h2N of 6.1% (SE = 11.6%), whilst FVC levels had a h2N of 30.6% (SE = 26.8%). AR, quantified by the loge dose-response slope to methacholine (DRS), had a h2N of 30.3% (SE = 12.3%). These data are consistent with the existence of important genetic determinants of the pathophysiological traits associated with asthma. Our study suggests that total and specific serum IgE levels, blood eosinophil counts and airways responsiveness to inhaled agonist are appropriate phenotypes for molecular investigations of the genetic susceptibility to asthma.

Adolescent↗