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Biomedical subjects

A W Musk

Publications and source records attributed to A W Musk.

At least 55 records · Page 3Linked to original sources
PubMed1999

Extended tumour necrosis factor/HLA-DR haplotypes and asthma in an Australian population sample.

BACKGROUND: Tumour necrosis factor (TNF) is a potent pro-inflammatory cytokine which is prominent in asthmatic airways. TNF shows genetic variations in secretion which are linked to polymorphisms in the TNF gene complex and the surrounding major histocompatibility (MHC) locus. These polymorphisms do not seem to be themselves functionally important. In these circumstances, the identification of disease associated haplotypes (combination of alleles on individual chromosomes) may narrow the search for polymorphisms which alter gene function. METHODS: TNF-308, LTalpha NcoI, and HLA-DRB1 polymorphisms were investigated for association with asthma, bronchial responsiveness, and medication use in 1004 subjects in 230 families from a general population sample. RESULTS: The common LTalpha NcoI*1/TNF-308*2/HLA-DRB1*03 haplotype, which was present in 11% of unrelated individuals, was weakly associated with asthma (OR = 1.38, p = 0.016, corrected for familial correlation). The rarer LTalpha NcoI*1/TNF-308*2/HLA-DRB1*02 haplotype, which was found in 0.6% of unrelated subjects, was more strongly associated with asthma (OR = 6.68, p = 0.002). This haplotype also showed association with bronchial hyperresponsiveness (OR = 21.9, p = 0. 0000) and the use of inhaled or oral steroids (OR 8.0, p = 0.04). CONCLUSIONS: The results of this study show only two extended TNF/HLA-DR haplotypes to be associated with asthma. The search for functional alleles responsible for an increased risk of asthma should concentrate on the LTalpha NcoI*1/TNF-308*2/HLA-DRB1*02 haplotype.

Adolescent↗
PubMed1999

Effect of asbestos-related pleural fibrosis on excursion of the lower chest wall and diaphragm.

To examine mechanisms responsible for reduced lung volumes (restriction) in asbestos-related pleural fibrosis (APF), we studied diaphragm function and lower rib-cage excursion in 26 subjects with previous asbestos exposure and no evidence of asbestosis. Using posteroanterior (PA) and lateral chest radiographs taken at residual volume and at 25%, 70%, and 100% vital capacity (VC) during a slow inspiratory maneuver, we measured fractional expansion of the lower rib cage (FErc), fractional shortening of the diaphragm (FSdi), and changes (Delta) in diaphragm dome height (Hdo) and subphrenic volume (Vdi). Vdi was estimated by measuring the major and minor axes of the subphrenic space at 1-cm intervals, assuming an elliptical cross-sectional shape, and correcting for the volume of spinal and paraspinal tissues. Seven subjects had no evidence of APF (control), 12 had pleural plaques (PP), and seven had diffuse pleural thickening with costophrenic obliteration (DPT). Over the range of VC, results (mean +/- SEM, normalized for height) in control subjects were VC = 101.2 +/- 4.0 % predicted and DeltaVdi = 326 +/- 8 ml/m(3), and for the right hemithorax and hemidiaphragm on the PA film, FErc = 0.07 +/- 0.02, FSdi = 0.32 +/- 0.02 and DeltaHdo = 0.8 +/- 0.2 cm/m. Relative to controls: DPT subjects had reduced VC (77.4 +/- 4.9%, p < 0.01), DeltaVdi (256 +/- 2 ml/m(3), p < 0.01), FErc (0.01 +/- 0.02, p < 0.01), FSdi (0.24 +/- 0.01, p < 0.001), and DeltaHdo (-0.9 +/- 0.06 cm/m, p < 0.01); PP subjects had reduced FSdi (0.25 +/- 0.01, p < 0.001) and DeltaVdi (233 +/- 47 ml/m(3), p < 0.01), and no difference in FErc, DeltaHdo, or VC. We conclude that restriction in DPT is due to obliteration of the zone of apposition, and that by limiting separation of the diaphragm from the rib cage during inspiration, this reduces volume contributed by motion of the diaphragm and lower rib cage. Reduction in the latter contribution was the main cause of restriction, because the reduction in volume contributed by the diaphragm was partly compensated by flattening of its dome.

Asbestos↗
PubMed1999

Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study.

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

Aged↗
PubMed1998

Vitamin A and cancer prevention I: observations in workers previously exposed to asbestos at Wittenoom, Western Australia.

Our aim was to describe a vitamin A-based cancer prevention program for former asbestos workers and to check for possible harmful effects by comparing rates of disease and death in study subjects with subjects who chose not to join. All subjects had been occupationally exposed to crocidolite at Wittenoom Gorge between 1943 and 1966; 1,677 subjects indicated interest in the program and 1,203 joined between June 1990 and May 1995. Comparison subjects consisted of 996 former workers known to be alive in Western Australia in 1990 who did not join the program. Program subjects were provided with annual supplies of vitamin A (either synthetic beta-carotene or retinol), help in quitting smoking and dietary advice. The comparison group received only mail contact. Both groups were followed up to December 1994 for vital status and cancer information, and rates of cancer and death from various causes were compared. Mortality in both groups was higher than expected (standardised mortality ratio 1.23 in program subjects and 1.67 in comparison subjects). After adjustment for age, smoking and asbestos exposure, the relative rates in participants compared with non-participants was below I for all examined cancers and causes of death. For mesothelioma and lung cancer, group differences increased with time from entry, whereas other differences dissipated with time. No significant side effects were reported. In conclusion, program participants had significantly lower mortality than non-participants, but the rates of the 2 groups converged with time.

Adult↗
PubMed1998

Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene.

Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.

Adult↗
PubMed1998

Fibroblast mitogens in bronchoalveolar lavage (BAL) fluid from asbestos-exposed subjects with and without clinical evidence of asbestosis: no evidence for the role of PDGF, TNF-alpha, IGF-1, or IL-1 beta.

Asbestosis is a fibrotic lung disease resulting from inhalation of asbestos fibres. Its pathogenesis is poorly understood but probably involves stimulation of fibroblast proliferation and collagen production by mediators released from inflammatory and resident lung cells. In vitro studies have implicate PDGF, TNF-alpha, IGF-1, TGF-beta, and IL-1 in asbestosis, but the role of these mediators in vivo is not known. This study aimed to characterize mediators in bronchoalveolar lavage (BAL) fluid from patients exposed to asbestos with (n = 24) or without (n = 34) asbestosis, compared with ten normal subjects. Human lung fibroblasts were exposed to serial dilutions of BAL fluids and the effects on fibroblast proliferation were assessed. The median mitogenic activity of BAL fluid from asbestos-exposed (17 per cent above medium control, range 3-44 per cent) and asbestosis (14 per cent, range 2-60 per cent) groups was higher than that of BAL fluid from controls (10 per cent, range 2-20 per cent; P < 0.01 and P < 0.05, respectively), but there was no significant difference between the patient groups. The mitogenic activity of BAL fluids was not reduced by incubation with neutralizing antibodies to PDGF-AA, PDGF-AB, PDGF-BB, TNF-alpha, IGF-1, and IL-1 beta. We conclude that BAL fluids from patients exposed to asbestos contain mitogens for human lung fibroblasts, but that PDGF, TNF-alpha, IGF-1, or IL-1 beta do not contribute to this activity.

Adult↗
PubMed1998

A genome scan for loci influencing total serum immunoglobulin levels: possible linkage of IgA to the chromosome 13 atopy locus.

Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE levels. In this study, 80 nuclear families have been examined for linkage of total serum IgA, IgG and IgM levels to a genome-wide panel of microsatellite markers. Potential quantitative trait loci influencing IgA levels have been identified on chromosomes 10 and 13, and possible loci influencing IgG levels were found on chromosomes 3 and 13. No significant linkages to IgM levels were found. The linkage of IgA on chromosome 13 was to a marker previously linked to IgE responses (atopy). Linkage to IgG was in the same region but to a more distal marker. None of the factors known to influence immunoglobulin expression map to the loci identified in the present study. These loci are therefore likely to contain previously unrecognized components of the immunoregulatory system.

Chromosomes, Human, Pair 13↗
PubMed1998

Cytokine gene therapy or infusion as treatment for solid human cancer.

In the induction of tissue-directed immune responses, cytokines tend to be released within the affected tissues. We used two strategies to expose tumor tissues to continuous high levels of cytokines: First, a vaccinia interleukin (IL)2 recombinant was injected directly intratumorally 3-weekly at 10(7) pfus/dose in six patients with the solid tumor malignant mesothelioma (MM). No virus excretion was detectable. At each cycle vaccinia-IL-2 mRNA (SQ [semi-quantitative] reverse transcription polymerase chain reaction) was maximal 24-72 h following injection reduced at 8 days and faded by 21 days. No tumor regression occurred. Second, based on the success of granulocyte macrophage colony-stimulating factor (GM-CSF) in gene transfer experiments, we conducted a study using continuous intratumoral GM-CSF infusion in eight patients with MM using a portable pump at doses of 10 micro/cg/24 h over 8 weeks. Systemic neutrophil agglutination and local catheter-related difficulties occurred. Two patients demonstrated tumor necrosis, one of whom had a marked progressive mononuclear cell infiltration of the tumor associated with a partial response (>50% reduction in tumor area). Murine studies using our MM model in CBA and BALB/C mice have demonstrated that B7-1 and allo-class I transfections induce strong tumor-specific cytotoxic T lymphocyte responses: GM-CSF, IL-12, and IL-2 induced mixed nonspecific plus specific responses, whereas B7-2 and class II transfections were not effective. We conclude that increased intratumoral cytokine concentrations can be generated using both gene transfer and cytokine infusion approaches; however, both have their limitations and, at this stage, have not produced dramatic antitumor effects in humans.

Cytokines↗
PubMed1998

Intralesional cytokine therapy in cancer: a pilot study of GM-CSF infusion in mesothelioma.

Systemic cytokine therapy in cancer has major side effects, and we reasoned that the local infusion of cytokines into tumors could induce local immunologic responses with minimal toxicity and potentially strong systemic anticancer effects. This study investigated the toxicity and effectiveness of intralesional granulocyte/macrophage-colony-stimulating factor (GM-CSF) infusion in solid-tumor masses. We studied 14 patients (12 men, two women) with malignant mesothelioma (MM), aged 60 years (range, 46-70 years), with stage 2 disease, in whom the tumor was of sufficient size and accessibility for an intralesional catheter to be inserted. Recombinant human GM-CSF (Molgramostim; Schering Plough) was infused intralesionally for 8 weeks, by using a portable pump, at a dose of 2.5-10 micrograms/kg/day. One patient using GM-CSF developed histologically confirmed necrosis of tumor surrounding the distal catheter, one developed a marked lymphocytic infiltrate in the tumor and had a partial response measured by chest computed tomography (CT) scan, 10 progressed, and three had no response. Neutrophilia with morphologic evidence of neutrophil activation and clinical features suggestive of neutrophil plugging of blood vessels occurred at doses > 5 micrograms/kg/day. In vitro, GM-CSF doubled human neutrophil/CD11b/CD18 expression, suggesting that neutrophil clumping as seen in vivo might be due to integrin upregulation. Intralesional infusion of cytokines is feasible but can be associated with systemic toxicity and has considerable technical problems. It produces a localized immune reaction with tumor regression in a minority of patients.

Aged↗
PubMed1998

Increased perception of airway narrowing in patients with mild asthma.

To compare the perception of airway narrowing of nonasthmatic subjects with those having wheeze or mild asthma (doctor-diagnosed), the relationship between FEV1 and breathlessness was examined in 123 subjects from a general population sample. Scores for breathlessness, using the Borg scale, were recorded before and after inhaling incremental doses of methacholine to a maximal dose of 196 mcmol or a maximum change in FEV1 of 50%. A history of asthma symptoms, including wheeze in the previous 12 months, and doctor-diagnosed asthma was obtained by questionnaire. At any given level of FEV1 there was wide variation in Borg scores between subjects, however median Borg scores and the mean slope of Borg score on FEVI was greater in the asthmatic subjects or those with wheeze compared with nonasthmatic subjects or those without wheeze. In both nonasthmatic and asthmatic subjects, those with airway hyperresponsiveness had increased maximum symptom scores and maximum changes in FEVI, but similar Borg scores relative to change in FEVI, compared with those without hyperresponsiveness. We conclude that the perception of mild and moderate degrees of airway narrowing varies widely between individuals but is increased in subjects with a history of mild asthma or wheeze in the last 12 months, independently of airway responsiveness.

Adult↗
PubMed1998

Silica, compensated silicosis, and lung cancer in Western Australian goldminers.

OBJECTIVES: Silica has recently been reclassified as carcinogenic to humans based largely on the observed increase in rates of lung cancer in subjects with silicosis. Other recent reviews have arrived at different conclusions as to whether silicosis or silica itself is carcinogenic. This study aims to examine exposure-response relations between exposure to silica and subsequent silicosis and lung cancer in a cohort of goldminers. METHODS: 2,297 goldminers from Kalgoorlie in Western Australia were examined in 1961, 1974, and 1975. Data were collected on respiratory symptoms, smoking habits, and employment history. Subjects were followed up to the end of 1993. Survival analyses for lung cancer mortality and incidence of compensated silicosis were performed with age and year matched conditional logistic regression analyses. RESULTS: 89% of the cohort were traced to the end of 1993. 84% of the men had smoked at some time and 66% were current smokers. 1386 deaths occurred during the follow up period, 138 from lung cancer, and 631 subjects were compensated for silicosis. A strong effect of smoking on mortality from lung cancer, and a smaller effect on the incidence of compensated silicosis was found. There was a strong effect of duration and intensity of exposure on the incidence of silicosis. The risk of mortality from lung cancer increased after compensation for silicosis. Of all direct measures of exposure to silica, only log cumulative exposure was significantly related to incidence of lung cancer, but this effect disappeared once the onset of silicosis was taken into account. CONCLUSIONS: The incidence of silicosis was clearly related to exposure to silica and the onset of silicosis conferred a significant increase in risk for subsequent lung cancer, but there was no evidence that exposure to silica caused lung cancer in the absence of silicosis.

Adolescent↗
PubMed1998

Environmental exposure to crocidolite and mesothelioma: exposure-response relationships.

This study aimed to estimate exposure-response relationships for mesothelioma and environmental exposure to crocidolite. All 4,659 former residents of Wittenoom, Western Australia (WA) who lived there between 1943 and 1993 for at least 1 mo and were not directly employed in the crocidolite industry, were followed-up through the WA death, cancer and mesothelioma registries, electoral rolls, and telephone books. In 1992, all subjects who should be traced were sent a questionnaire. Exposure levels were estimated from results of periodic environmental surveys and duration of residence. Incidence rates were standardized to the World Population and Cox Regression was used to estimate the effects of exposure on incidence. To the end of 1993, 27 cases of mesothelioma were diagnosed. Mesothelioma cases stayed longer at Wittenoom, had a higher average intensity of exposure, and a higher cumulative exposure to crocidolite than control subjects. The standardized incidence of mesothelioma was 260 per million person-years, and was similar for males and females. The rate increased significantly with time from first exposure, duration of exposure and cumulative exposure. At these levels of crocidolite exposure, there is a significantly increased risk of mesothelioma, which is dose-dependent.

Adult↗
PubMed1998

Respiratory symptoms and lung function in aborigines from tropical Western Australia.

To estimate the prevalence of respiratory symptoms, bronchial hyperresponsiveness, smoking, and atopy in a population of Australians of Aboriginal descent (AAD), to determine the association of these and other factors with lung function, and to compare levels of lung function of AAD with Australians of European descent (AED) according to age and height, and to explore reasons for their differences, we conducted a study of 96 male (41 of whom were under 18 yr of age) and 111 female (48 of whom were under 18 yr of age) AAD living in a single remote tropical community in 1993. This population provided data on age, height, and lung function. A modified British Medical Research Council (MRC) questionnaire on respiratory symptoms and smoking was administered. FEV1, FVC, height, age, and bronchial responsiveness to inhaled methacholine were measured. Atopic status was assessed by skin prick tests for eight common allergens. Age- and sex-adjusted lung function was similar to that of other AAD groups and lower than in AED. For children, lung function increased less with increasing height in AAD than in AED. Lung function was reduced in adult AAD as compared with adult AED, although it was not possible to determine statistically whether lung function started to decline at an earlier age or declined faster with increasing age in AAD. A history of asthma, smoking, dyspnea, cough, or sputum production; atopic status; and increased bronchial responsiveness were all associated with lower levels of lung function. Differences in lung function between AAD and AED appear to be determined by characteristics that may be inherited, as well as by adverse external influences.

Adolescent↗
PubMed1997

Fc epsilon R1-beta polymorphism and total serum IgE levels in endemically parasitized Australian aborigines.

Endemic helminthic infection is a major public-health problem and affects a large proportion of the world's population. In Australia, helminthic infection is endemic in Aboriginal communities living in tropical northern regions of the continent. Such infection is associated with nonspecific (polyclonal) stimulation of IgE synthesis and highly elevated total serum IgE levels. There is evidence that worm-infection variance (i.e., human capacity of resistance) and total serum IgE levels may be related to the presence of a major codominant gene. The beta chain of the high-affinity IgE receptor, Fc epsilon R1-beta, has been previously identified as a candidate for the close genetic linkage of the 11q13 region to IgE responses in several populations. We show a biallelic RsaI polymorphism in Fc epsilon R1-beta to be associated with total serum IgE levels (P = .0001) in a tropical population of endemically parasitized Australian Aborigines (n = 234 subjects). The polymorphism explained 12.4% of the total residual variation in serum total IgE and showed a significant (P = .0000) additive relationship with total serum IgE levels, across the three genotypes. These associations were independent of familial correlations, age, gender, racial admixture, or smoking status. Alleles of a microsatellite repeat in intron 5 of the same gene showed similar associations. The results suggest that variation in Fc epsilon R1-beta may regulate IgE-mediated immune responses in this population.

Alleles↗
PubMed1997

Risk factors for the development of non-response to first-line treatment for tuberculosis in southern Vietnam.

BACKGROUND: Acquired resistance to standard chemotherapy for tuberculosis (TB) is an increasing problem worldwide. Vietnam has one of the highest incidences of TB and also has a large population of potential migrants to other countries. Since 1979 the International Organisation for Migration (IOM) has been running a supervised programme of TB treatment for intending migrants from Vietnam where few facilities for bacteriological culture and sensitivity testing exist. This study aimed to assess the most important factors for predicting non-response to first-line treatment as treatment starts and whether any further indicators occur during the course of treatment which may enable more accurate prediction of non-response. METHODS: In all, 130 subjects failing to respond to first-line therapy (cases) between 1990 and 1995 were compared with 673 subjects who responded to therapy (controls) on various demographic and clinical characteristics using logistic regression to create a prognostic index. Variables analysed included the patient history of past TB treatment, weight, age, sex and radiological and bacteriological findings. All subjects also tested negative for HIV status. RESULTS: The chief markers of successful response were x-ray signs and degree of sputum smear positivity. These markers provided a prognostic index with an optimal cutoff providing about 70% sensitivity and 80% specificity. Incorporating further measures obtained through the first 3 months of treatment improved the sensitivity to 80%. CONCLUSION: While this study enabled prediction of the majority of subjects failing to respond to first-line therapy, other factors need to be assessed before recommendations for altering treatment regimens can be made. The prognostic index could be useful in assessing subjects for closer supervision.

Adult↗
PubMed1997

Comparison of oral bambuterol and terbutaline in elderly patients with chronic reversible airflow obstruction.

Bambuterol, a carbamate prodrug of terbutaline, is the first once-daily oral beta 2-agonist. The effect/side effect ratio of bambuterol oral solution was compared with terbutaline mixture in elderly patients with chronic reversible obstructive airways disease. The study was of a double-blind, crossover, randomized design and consisted of a 4-7-day run-in period followed by four consecutive treatment periods each of 2 weeks. The treatments were bambuterol solution 20 mg nocte (B20), 10 mg nocte (B10), terbutaline mixture 3 mg t.i.d., (T), and placebo solution (P). Patients measured daily peak expiratory flow rate (PEFR), asthma symptoms, use of inhaled beta 2-agonist, and tremor. Of 84 patients, 66 completed all periods. Mean age was 67 years (60-90), basal FEV1 1.49 L, and reversibility of FEV1 30%. Ninety-four percent of the patients used inhaled/oral steroids in constant dosage. All treatments were significantly more effective than placebo. B20 resulted in higher morning PEFR than T (306 +/- 2.9 L/min vs. 297 +/- 2.9 L/min), while B10 gave equivalent results to T. No differences were seen in the use of inhaled beta 2-agonist. Less shortness of breath was experienced during the night with B20 and during the day with B10 compared with placebo. Both B20 and T produced more tremor than B10 and P. In elderly patients with chronic reversible airways obstruction once-daily bambuterol (10-20 mg) has a better effect/side effect ratio than 3 mg terbutaline thrice daily.

Administration, Oral↗
PubMed1996

A genome-wide search for quantitative trait loci underlying asthma.

Asthma now affects one child in seven in the United Kingdom. Most cases (95%) of childhood asthma are associated with atopy, the immunoglobulin E (IgE)-mediated familial syndrome of allergic asthma, eczema and rhinitis. Segregation analysis has consistently suggested the presence of major genes influencing atopy and IgE levels, with the expectation that these genes may be identified by positional cloning or the examination of candidate genes. Here we report the results of a genome-wide search for linkage to one qualitative and four quantitative traits associated with allergic (atopic) asthma. We have identified six potential linkages (P<0.001), five of which are to quantitative traits. Monte Carlo simulations show that 1.6 false-positive linkages at this level of significance would be expected from the data. One linkage, to chromosome 11q13, has been established previously. Three of the new loci show evidence of linkage to a second panel of families, in which maternal effects and pleiotropy of linked phenotypes are seen. The results demonstrate the extent and the complexity of the genetic predisposition to asthma.

Adolescent↗