Many reports of RCTs give insufficient data for Cochrane reviewers.
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Data Collection↗
Biomedical subjects
E H Walters
Publications and source records attributed to E H Walters.
Comparison of patients with asthma managed in general practice and in a hospital clinic.
OBJECTIVES: To compare knowledge and attitudes about asthma, self-management skills and impact of asthma on quality of life between patients managed in general practice (GP) and in a hospital clinic. DESIGN: Cross-sectional survey with six months' follow-up. PATIENTS AND SETTING: 105 adults with asthma: 61 from the Alfred Hospital Asthma and Allergy Clinic, Melbourne, and 44 from nearby general practices, in 1994-1995. MAIN OUTCOME MEASURES: Patient sociodemographic and clinical characteristics; patient knowledge, attitudes and beliefs about asthma; self-management skills; and impact of asthma on quality of life. RESULTS: GP patients were more educated (P = 0.04) and more likely to smoke (P = 0.04) and to have mild asthma (P = 0.04) than hospital patients; they were less likely to use theophylline (P = 0.006) and to have exercise limitation (P = 0.03), and had fewer previous hospital admissions (P = 0.01). Impact of asthma on quality of life was greater in the hospital group than in the GP group. At baseline, the GP group were less likely to have written asthma action plans (P = 0.018), and were less able to manage rapid onset attacks than the hospital group (P = 0.02). More subjects in the hospital group than the GP group felt their asthma was severe (P = 0.02) and were optimistic about their asthma improving (P = 0.03). GP patients increased their knowledge about asthma significantly (P = 0.002) over six months. CONCLUSIONS: Patients with asthma managed in general practice and in hospital differ in clinical parameters, quality of life and attitudes to asthma. Future educational initiatives should take such differences into account.
Adult↗
Influence of pulmonary capillary wedge pressure on central apnea in heart failure.
BACKGROUND: Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilation-related hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity. METHODS AND RESULTS: Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (n=33), obstructive apnea (n=20), or nonapnea groups (apnea-hypopnea index [AHI] <5 events per hour). Mean PCWP was significantly greater in the central than in the obstructive and nonapnea groups (mean+/-SEM [range]: 22. 8+/-1.2 [11 to 38] versus 12.3+/-1.2 [4 to 21] versus 11.5+/-1.5 [3 to 28] mm Hg, respectively; P<0.001). Within the central apnea group, PCWP correlated with the frequency and severity of central apnea (AHI: r=0.47, P=0.006) and degree of hypocapnia (PaCO2: r=-0.42, P=0. 017). Intensive medical therapy in 7 patients with initially high PCWP and central apneas reduced both PCWP (29.0+/-2.6 [20 to 38] to 22.0+/-1.8 [17 to 27] mm Hg; P<0.001) and central apnea frequency (AHI) (38.5+/-7.7 [7 to 62] to 18.5+/-5.3 [1 to 31] events per hour; P=0.005). CONCLUSIONS: PCWP is elevated in CHF patients with central apneas compared with those with obstructive apnea or without apnea. Moreover, a highly significant relationship exists between PCWP, hypocapnia, and central apnea frequency and severity.
Adolescent↗
Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4delta2.
BACKGROUND: The human IL4 gene, has been shown to express the alternatively spliced messenger (m)RNA IL-4delta2. IL-4delta2 is missing the entire sequence from exon 2 and has been identified as an IL-4 receptor antagonist. OBJECTIVE: We sought to distinguish IL-4 and IL-4delta2 mRNA in respiratory tract tissue for the first time. METHODS: A novel competitive PCR assay was established with primers designed on either side of the alternative splice junction of the IL4 gene, allowing the simultaneous quantitation of both IL-4 and IL-4delta2 mRNA from one reaction. RESULTS: IL-4 and IL-4delta2 were differentially expressed in 4 nasal polyps. No difference was seen in endobronchial biopsy specimens for IL-4 mRNA expression between control subjects (median, 2.8 x 10(2) copies/microg RNA; range, 0-3.7 x 10(3) copies/microg RNA) and asthmatic subjects (median, 1.4 x 10(2) copies/microg RNA; range, 0-4.7 x 10(2) copies/microg RNA). However, significantly more asthmatic subjects (6 of 9) than control subjects (1 of 7) expressed IL-4delta2 (P =. 036). Expression of IL-4 variants was unaffected by atopic status. CONCLUSIONS: Given that IL-4delta2 is an IL-4 receptor antagonist, these results indicate that it is crucial to be able to distinguish IL-4delta2 from IL-4 when assessing IL4 gene expression. Increased expression of IL-4delta2 in stable asthmatic subjects suggests that the balance of IL-4 and IL-4delta2 may modulate asthmatic inflammation.
Adult↗
Airway vascular changes in lung allograft recipients.
BACKGROUND: In asthma there has been increasing interest in the contribution of airway microvasculature to airway wall thickness and lumenal narrowing. Post-lung transplant, the survival of the donor airway is generally dependent on mixed-venous blood flow from pulmonary artery collaterals associated with the discontinuation of the bronchial circulation. This may lead to an altered vasculature of the airways post transplant, which may contribute to airflow limitation. METHODS: Endobronchial biopsies were taken from the lower lobe sub-carinae in 22 lung transplant recipients (LTR), 8 with Bronchiolitis Obliterans Syndrome (BOS), 14 without, and 14 controls. Seven microm frozen sections were stained for type IV collagen with a monoclonal antibody, using an indirect immunoperoxidase method. Bronchial vessels were identified by typical staining of type IV collagen in the true basement membrane supporting the endothelium. The number of vessels per mm2 of submucosa to a depth of 150 microm below the basement membrane, the percent vascularity and average vessel size were quantified using a computerised image analyser. RESULTS: Compared to the controls, a higher percent vascularity was found in LTR both with and without BOS (p < 0.05). In the BOS group, the percent best FEV1.0 decreased exponentially, in association with increased airway vessel size (r2 = 0.67, p = 0.01). CONCLUSIONS: These findings suggest that increased airway vascularity is a feature of the allograft airways post transplant. This may be a result of the relative hypoxia and hypercarbia in the blood supplying the airways from the pulmonary artery collaterals or of the chronic inflammatory process in the airways. These changes in vascularity could contribute to airflow limitation in BOS.
Adult↗
Modulatory effects of alveolar macrophages on CD4+ T-cell IL-5 responses correlate with IL-1beta, IL-6, and IL-12 production.
Increasing evidence suggests that the pattern of T-cell cytokine production can be modulated by antigen presenting cell (APC)-derived factors during the cell interactions. Recently, it has been shown that alveolar macrophages (AMs) from atopic asthmatics (AA) but not atopic nonasthmatics (AN) enhance interleukin (IL)-5 production by CD4+ T-cells. The present study compared AM production of IL-1beta, IL-6, and IL-12, as well as their associated functional capacity to influence IL-5 production by allergen-specific CD4+ T-cells in 10 AA, 10 AN, and nine nonatopic control subjects (C). AMs from AA showed a relatively high production of IL-1beta and IL-6 (p<0.05) and a relatively low secretion of IL-12 compared to C, whereas AMs from AN and C behaved similarly. This study confirmed previous findings that co-culture with AMs augments IL-5 production from allergen-stimulated CD4+ T-cells only in AA and not in nonasthmatics even if they are atopic. On the other hand, stimulation with allergen alone did not enhance IL-5 production by CD4+ T-cells in either AA nor AN. AM-induced changes in CD4+ T-cell IL-5 production upon allergen stimulation significantly correlated with their ability to produce IL-1beta (r=0.59, p<0.01), IL-6 (r=0.56, p<0.01), and inversely with IL-12 (r=-64, p=0.002) in all atopic subjects, and even more closely with the ratio of IL-12/IL-1beta (r=-0.75, p<0.001) and IL-12/IL-6 production (r=-0.81, p<0.001) in these subjects. These findings suggest that the role of alveolar macrophages from atopic asthmatics in enhancing interleukin-5 production by allergen-specific CD4+ T-cells is due, at least partly, to their aberrant production of interleukin-1beta, interleukin-6, and particularly of interleukin-12.
Adult↗
A critical evaluation of the Mefar dosimeter.
Multicentre studies of airway responsiveness (AR) are increasingly important tools in asthma epidemiology. Because comparisons of AR are made between centres it is essential that measurement techniques are accurate and standard. This study investigated the Mefar dosimeter which is currently used in the 35 centre European Community Respiratory Health Survey (ECRHS) with the next phase currently being planned. Significant differences were found in driving pressures and aerosol outputs between the three Mefar dosimeters in the laboratory. A linear relationship was also found between driving pressure and aerosol output (R2=0.96). These differences are important as they may lead to variations between centres of < or =35% in the drug dose delivered in AR measurement, which could potentially diminish the power of individual study centres to accurately detect national differences in AR. Dosimeter driving pressure and nebulizer output should be standardized in future studies of airway responsiveness. With relatively simple quality control measures in place it is believed that the Mefar dosimeter can produce reliable between-centre longitudinal data with an increase in the accuracy of these important studies.
Aerosols↗
Residential characteristics influence Der p 1 levels in homes in Melbourne, Australia.
BACKGROUND: Exposure to house dust mite (HDM) allergens is an important risk factor for childhood asthma. Knowledge of environmental determinants of HDM allergen levels is essential before designing rational avoidance measures. AIM: To investigate the effect of domestic characteristics on HDM allergen (Der p 1) levels in Melbourne homes. METHODS: Dust was collected from bed and floor of the bedrooms in 485 houses over a period of one year. Dust was analysed for Der p 1 levels using an enzyme-linked immunosorbent assay. Temperature and relative humidity were measured at the visit. Details of residential characteristics were collected using a questionnaire. Statistically significant predictors of Der p 1 levels (P < 0.05) were identified using multiple linear regression. RESULTS: High levels of Der p 1 were observed in the floors (geometric mean 17.2 microg/g fine dust) as well as in the beds (geometric mean 20.3 microg/g fine dust). Der p 1 levels in the floor dust were significantly lower in winter and spring. They were higher in houses built before 1980 and those with central heating, weather board walls, damp bedrooms or fitted old wool carpets. Der p 1 levels in bed dust were significantly higher in houses built before 1980, with wooden floors built on stumps, with high relative humidity, with visible mould in the room, in beds with an old mattress or in beds without a quilt. CONCLUSIONS: We would encourage construction of homes without carpets, wooden floors on stumps or weather board walls.
Allergens↗
Prevalence and residential determinants of fungi within homes in Melbourne, Australia.
BACKGROUND: Recent epidemiological studies suggest that the adverse respiratory health effects caused by the inhalation of fungal propagules are substantial. Knowledge of the prevalence and environmental determinants of indoor fungal levels is essential in designing effective avoidance measures. AIM: To investigate the prevalence of fungi and the influence of residential characteristics on levels of fungi within homes in Melbourne, Australia. METHODS: Floor dust and air samples were collected from bedrooms in 485 houses over 1 year. The dust was analysed for ergosterol, a marker of cumulative fungal biomass exposure. Total and genera-specific fungal propagules were identified in air samples. Details of the relevant residential characteristics were documented using a questionnaire. Independent predictors (P < 0.05) of ergosterol and total fungal propagules were identified by multiple linear regression. RESULTS: Fifty-five percent of the houses had viable fungal propagules exceeding 500 CFU/m3. Cladosporium and Penicillium were identified as the most prevalent and abundant fungal genera in indoor air. The median ergosterol level in bedroom floor was 3.8 microg/g of dust. Multivariate analysis showed that total fungal propagules in indoor air were lower in bedrooms with a ceiling fan, without visible mould, and those that were more frequently vacuumed, had a solid fuel fire, had windows closed at the time of the sampling or lacked pets. The presence of more than one cat had the greatest effect on total fungal propagules. Ergosterol levels were significantly lower in homes without old fitted carpets, visible mould or pets and those with frequent airing and regular use of an extractor fan in the kitchen. Old wall-to-wall carpets had the greatest effect on ergosterol. CONCLUSIONS: High indoor fungal exposures were associated with infrequent ventilation or vacuuming, presence of pets, visible mould and old carpets.
Adult↗
A cost-analysis of two approaches to infection control in a lung function laboratory.
BACKGROUND: The Thoracic Society of Australia and New Zealand (TSANZ) guidelines for infection control in respiratory laboratories are based on a 'Universal Precautions' approach to patient care. This requires that one-way breathing valves, flow sensors, and other items, be cleaned and disinfected between patient use. However, this is impractical in a busy laboratory. The recent introduction of disposable barrier filters may provide a practical solution to this problem, although most consider this approach to be an expensive option. AIM: To compare the cost of implementing the TSANZ infection control guidelines with the cost of using disposable barrier filters. METHODS: Costs were based on the standard tests and equipment currently used in the lung function laboratory at The Alfred Hospital. We have assumed that a barrier filter offers the same degree of protection against cross-infection between patients as the TSANZ infection control guidelines. Time and motion studies were performed on the dismantling, cleaning, disinfecting, reassembling and re-calibrating of equipment. Conservative estimates were made as to the frequency of replacing pneumotachographs and rubber mouthpieces based on previous equipment turnover. Labour costs for a scientist to reprocess the equipment was based on $20.86/hour. The cost of employing a casual cleaner at an hourly rate of $14.07 to assist in reprocessing equipment was also investigated. The new high efficiency HyperFilter disposable barrier filter, costing $2.95 was used in this cost-analysis. RESULTS: The cost of reprocessing equipment required for spirometry alone was $17.58 per test if a scientist reprocesses the equipment, and $15.56 per test if a casual cleaner is employed to assist the scientist in performing these duties. In contrast, using a disposable filter would cost only $2.95 per test. Using a filter was considerably less expensive than following the TSANZ guidelines for all tests and equipment used in this cost-analysis. CONCLUSIONS: The TSANZ infection control guidelines are expensive and impractical to implement. However, disposable barrier filters provide a practical and inexpensive method of infection control.
Australia↗
A reliable and valid home visit report for studies of asthma in young adults.
Validated instruments are not available to assess the residential characteristics. The aim of this study was to assess the reliability and validity of an interviewer-administered home visit report. The validity of 48 items in the Home Visit Report was examined against: observations made by a researcher, measurements of relative humidity, cat allergen, and ergosterol, a biomaker of fungal exposure and a biochemical test. Test-retest reliability of 10 fixed residential characteristics was assessed comparing the responses obtained in the main study with the pilot study, Kappa, ANOVA and Wilcoxon Rank Sum tests were applied to assess the agreement and P < 0.05 was considered as statistically significant. Among 44 items examined for the validity against observations, there was a perfect or almost perfect agreement in 21 (kappa = 0.9-1) and substantial agreement (kappa = 0.6-0.8) in 19. Higher cat allergen levels were observed with cat ownership and cat being allowed indoors. Observed condensation was associated with relative humidity and observed mould was associated with ergosterol levels. The agreement on the type of carpet and the test was substantial (kappa = 0.6). Among 10 items examined for reliability, there was a perfect or almost perfect agreement in 9 (kappa = 0.9-1) and substantial agreement (kappa = 0.7) in one. In conclusion, the Home Visit Report validated in this study provides reliable and valid data.
Adult↗
Vascularity in asthmatic airways: relation to inhaled steroid dose.
BACKGROUND: There is an increase in vascularity in the asthmatic airway. Although inhaled corticosteroids (ICS) are an effective anti-inflammatory treatment in asthma, there are few data on any effects on structural changes. METHODS: Endobronchial biopsy specimens from seven asthmatic subjects not receiving ICS and 15 receiving 200-1500 microg/day beclomethasone dipropionate (BDP) were immunohistochemically stained with an anti-collagen type IV antibody to outline the endothelial basement membrane of the vessels. These were compared with biopsy tissue from 11 non-asthmatic controls (four atopic and seven non-atopic). RESULTS: There was a significant increase in the density of vessels (number of vessels/mm2 of lamina propria) in the asthmatic subjects not on ICS compared with non-asthmatic controls (mean 485 (interquartile range (IQR) 390-597) versus 329 (IQR 248-376) vessels/mm2, p<0.05; 95% CI for the difference 48 to 286). There was no significant difference between asthmatic subjects on ICS and those not on ICS or control subjects in the number of vessels/mm2 (mean 421 (IQR 281-534)). However, patients who received >/=800 microg/day BDP tended to have a reduced number of vessels/mm2 compared with patients not on ICS and those receiving </=500 microg/day BDP (mean 366 (IQR 153-608) versus 494 (IQR 391-583), p = 0.08; 95% CI for the difference -31 to 288). Similarly, there was an increase in the percentage of lamina propria occupied by vessels in asthmatic patients not on ICS compared with controls (mean 15.6% (IQR 13.1-18.0) versus 10.1% (IQR 8.4-13.3), p<0.01; 95% CI for the difference 2.4 to 9.3) but a significant decrease in the percentage of lamina propria occupied by vessels was detected in asthmatic patients on ICS (mean 11.4% (IQR 9.1-14.9), p<0.01; 95% CI for the difference 0.7 to 7.7) compared with those not on ICS. The density of vessels correlated significantly with both airway hyperresponsiveness and percentage change in forced expiratory volume in one second (FEV1) after bronchodilator (r = -0. 38 for PD20 methacholine and r = 0.49 for change in percentage FEV1 after bronchodilator versus number of vessels/mm2, p<0.05). CONCLUSION: These findings suggest that ICS, especially at higher doses, may reduce airway wall vascularity in asthmatic subjects but further longitudinal intervention studies are required to confirm this suggestion.
Administration, Inhalation↗
Mutational analysis of the high affinity immunoglobulin E receptor beta subunit gene in asthma.
BACKGROUND: The gene for the beta subunit of the high affinity receptor for immunoglobulin E (FcepsilonRI-beta) on chromosome 11q13 is linked with clinical asthma and certain mutations have been identified. A study was undertaken to identify DNA variation in the FcepsilonRI-beta gene in a population sample in which linkage between 11q13 and asthma was explained by bronchial hyperreactivity (BHR) but not atopy. METHODS: DNA samples from 71 subjects with asthma, atopy, or BHR were analysed. The complete coding region, some of the introns, and some of the 5' untranscribed region of the FcepsilonRI-beta gene were sequenced. RESULTS: In the subjects studied there were no deviations from the published sequence in any of the seven coding exons of the FcepsilonRI-beta gene. In particular, the three previously reported mutations (Ile181, Leu183, Glu237) were not detected. Two new polymorphisms were discovered, one at position 243 in the 5' untranscribed region and one at position 4390 in intron III. Neither of these variants showed significant association with asthma, atopy, or BHR. CONCLUSIONS: These results suggest that, in the population studied, linkage of asthma and BHR to 11q13 is not explained by mutations in the FcepsilonRI-beta gene. Other mutations in the non-coding region of this gene or in adjacent genes must explain the linkage findings in this study.
Asthma↗
Evaluation of a randomised controlled trial of adult asthma education in a hospital setting.
BACKGROUND: Although patient education is a key step in the Australian Asthma Management Plan, its impact has not been assessed in a hospital outpatient asthma clinic. METHODS: A controlled trial was undertaken in 125 adults with asthma recruited from the Alfred Hospital Asthma and Allergy Clinic and randomly allocated to an intervention (n = 64) or control (n = 61) group. Subjects in the intervention group attended three education sessions, each of 90 minutes duration, spread over three successive weeks. Asthma knowledge, quality of life, self-management skills, and attitudes and beliefs about asthma were assessed by questionnaires at baseline and after six months. The intervention group was also assessed immediately after the three education sessions. The control group was evaluated after six months of usual care. RESULTS: Asthma knowledge improved significantly in the intervention group after three education sessions (p = 0.0001) and this was retained six months later (p = 0.03). The impact of asthma on quality of life decreased significantly immediately after intervention (p = 0.03) but this was not maintained six months later (p = 0.35). On the other hand, the intervention had little impact on self-management skills or attitudes and beliefs about asthma. However, the control group had also improved their knowledge, quality of life and self-management skills after six months of usual care. The difference in mean change in knowledge score at six months between the intervention and control groups was not significant (p = 0.51). CONCLUSIONS: In contrast to some other studies, a limited asthma education programme in a hospital outpatient setting had a positive impact on patients' knowledge of asthma, but not on their quality of life, self-management skills, or attitudes and beliefs about asthma.
Adult↗
Skeletal muscle oxidative capacity, fiber type, and metabolites after lung transplantation.
Lung transplant (LTx) recipients have a low peak work rate, peak oxygen consumption (V O2peak), and early lactate threshold on incremental exercise. We hypothesized that LTx recipients have reduced oxidative function and altered fiber type proportion in peripheral skeletal muscle. Seven stable LTx recipients and seven age- and sex-matched control subjects were studied. Incremental exercise testing with arterialized venous sampling and a resting quadriceps femoris punch muscle biopsy were performed. Muscle specimens were analyzed for fiber type proportion, metabolites, oxidative and glycolytic enzyme activities, and mitochondrial ATP production rate (MAPR) using standard techniques. The results showed that mean V O2peak in LTx recipients was 52% of control subjects. Compared with the control subjects, LTx skeletal muscle exhibited: (1) a lower MAPR; (2) lower activity of the mitochondrial enzymes glutamate dehydrogenase (GDH), citrate synthase (CS), 2-oxogluterate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA-dehydrogenase (HAD). There was no difference in the activities of anaerobic enzymes, except for higher phosphofructokinase activity; (3) a lower proportion of type I fibers; (4) a higher lactate and inosine monophosphate (IMP) content and a lower ATP content at rest indicating a high reliance on anaerobic metabolism. The reduced type I fiber proportion and severely reduced mitochondrial oxidative capacity may play an important role in exercise limitation after LTx.
Adult↗
Hypoxemia and hypercapnia during exercise and sleep in patients with cystic fibrosis.
BACKGROUND: In patients with cystic fibrosis (CF), it has been proposed that hypoxemia and hypercapnia occur during episodes of stress, such as exercise and sleep, and that respiratory muscle weakness because of malnutrition may be responsible. METHODS: Pulmonary function, respiratory muscle strength, and nutrition were assessed and correlated with the degree of hypoxemia and hypercapnia during exercise and sleep in 14 patients with CF and 8 control subjects. RESULTS: Despite no differences in maximum static inspiratory pressure (PImax) between the two groups, the CF group developed more severe hypoxemia (minimum oxyhemoglobin saturation [SpO2], 89 +/- 5% vs 96 +/- 2%; p < 0.001) and hypercapnia (maximum transcutaneous CO2 tension [PtcCO2], 43 +/- 6 vs 33 +/- 7 mm Hg; p < 0.01) during exercise. Similarly, during sleep, the CF group developed greater hypoxemia (minimum SpO2, 82 +/- 8% vs 91 +/- 2%; p < 0.005), although CO2 levels were not significantly different (maximum PtcCO2, 48 +/- 7 vs 50 +/- 2 mm Hg). Within the CF group, exercise-related hypoxemia and hypercapnia did not correlate with FEV1, residual volume/total lung capacity ratio (RV/TLC), PImax, or body mass index (BMI). Hypoxemia and hypercapnia during sleep correlated with markers of gas trapping (RV vs minimum arterial oxygen saturation [r = -0.654; p < 0.05]), RV vs maximum PtcCO2 (r = 0.878; p < 0.001), and RV/TLC vs maximum PtcCO2 (r = 0.790; p < 0.01) but not with PImax or BMI. CONCLUSION: Patients with moderately severe CF develop hypoxemia and hypercapnia during exercise and sleep to a greater extent than healthy subjects with similar respiratory muscle strength and nutritional status. Neither respiratory muscle weakness nor malnutrition are necessary to develop hypoxemia or hypercapnia during exercise or sleep.
Adult↗
A genetic twist to the beta-agonist 'debate'.
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Adrenergic beta-Agonists↗
Differential regulation of allergen-specific T(H2)- but not T(H1)-type responses by alveolar macrophages in atopic asthma.
BACKGROUND AND OBJECTIVE: Previous studies have suggested that quantitative differences in TH2-type cytokine responses in the airways are of particular importance in the pathogenesis of asthma. In this study we investigated whether alveolar macrophages (AMs) and peripheral blood monocytes (PMNs) are able to significantly influence the profiles of allergen-induced TH1 (IFN-gamma) and TH2 (IL-4 and IL-5) cytokine production by CD4+ T cells in atopic asthmatic subjects versus atopic nonasthmatic subjects and nonatopic normal subjects. METHODS: Peripheral blood CD4+ T cells were cultured alone or cocultured with either PMNs or AMs with allergen stimulation in the 3 groups. RESULTS: Although allergen stimulation did not change TH1 or TH2 cytokine responses in cultures of CD4+ T cells alone, the addition of PMNs to the cultures induced a significant increase in production of IL-4, IL-5, and IFN-gamma (P < .01 or P < .001) in atopic asthmatic subjects and atopic nonasthmatic subjects. However, PMNs induced a significant increase for IFN-gamma (P < .05) only in normal subjects. AMs from atopic asthmatic subjects significantly enhanced production of all 3 cytokines (P < .01 or P < .001), whereas the AMs from atopic nonasthmatic subjects significantly increased only production of IL-4 (P < .01) and IFN-gamma (P < .05) but not IL-5. Furthermore, IL-4 (P = .066) and IL-5 (P < .01) production in allergen-stimulated AM-CD4+ cell cocultures was higher in atopic asthmatic subjects but significantly lower in atopic nonasthmatic subjects (P < .05) as compared with the PMN-cocultures. For IFN-gamma, no difference was found between the AM and PMN cocultures in either atopic group. Allergen-stimulated IL-5 production in coculture with both AMs and PMNs inversely correlated with both baseline FEV1 percent predicted and PD20 methacholine in atopic asthmatic subjects (P < .05, P < .01, or P < .001). CONCLUSION: These data suggest that AMs from atopic asthmatic subjects but not atopic nonasthmatic subjects, play a significant role in airway pathogenic immunity through enhancing TH2-type cytokine production.
Adolescent↗