Severe Asthmatic Subjects Research Articles

Urinary concentrations of 15‐epimer of lipoxin A4 are lower in patients with aspirin‐intolerant compared with aspirin‐tolerant asthma

Although an abnormality in arachidonic acid metabolism may be responsible for aspirin-intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A(4) (LXA(4)) and the 15-epimer of LXA(4) (15-epi-LXA(4)) in relation to asthma severity in AIA subjects. The purpose of this study is to estimate urinary LXA(4) and the 15-epimer concentrations to investigate lipoxins in AIA. In this study, we examined AIA, aspirin-tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non-severe asthma subgroups. Urinary LXA(4), 15-epi-LXA(4) and leukotriene E(4) (LTE(4) ) were quantified using enzyme immunoassay after separating these compounds using high-performance liquid chromatography. The urinary LXA(4) concentration was significantly lower than the 15-epi-LXA(4) concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA(4) (P < 0.01) and higher urinary LTE(4) concentrations (P < 0.05) than the ATA group. Comparison of 15-epi-LXA(4) concentrations between the severe asthmatic and non-severe asthmatic subjects in the AIA and ATA groups revealed that the decreased 15-epi-LXA(4) concentration may be related to aspirin intolerance, but not asthma severity. Receiver operator characteristic curves demonstrated that the concentration ratio of LTE(4) to 15-epi-LXA(4) was superior to 15-epi-LXA(4) concentration and LTE(4) concentration as a predictive factor for aspirin intolerance. We have demonstrated for the first time that urinary 15-epi-LXA(4) concentration is significantly higher than LXA(4) concentration in both the AIA and ATA groups. 15-Epi-LXA(4) concentration was significantly lower in the AIA group with an increased urinary LTE(4) concentration than in the ATA group. An imbalance between proinflammatory cysteinyl-leukotrienes and anti-inflammatory 15-epi-LXA(4) may be involved in AIA pathogenesis.

S44 Increased expression of immunoreactive thymic stromal lymphopoetin in severe asthma

BackgroundThymic stromal lymphopoetin (TSLP) is a cytokine implicated in the pathophysiology of asthma through two pathways: a TSLP-OX40L-T cell axis and a TSLP-mast cell axis. Whether these pathways operate in...

Prostaglandin E2 and cysteinyl leukotriene concentrations in sputum: association with asthma severity and eosinophilic inflammation

Inflammation of the airways in asthma is associated with the production of cysteinyl leukotrienes (cysLT), prostaglandin (PG)E(2), 8-isoprostane, nitric oxide and other mediators. However, the relationship between asthma severity or eosinophilic inflammation and the concentrations of mediators in sputum is unclear. To assess sputum PGE(2), cysLT, 8-isoprostane and nitrate concentrations, as well as urinary leukotriene (LT)E(4) and 9alpha,11beta-prostaglandin (PG)F(2) concentrations, in patients with differing severities of asthma and eosinophilic or non-eosinophilic airway inflammation. Inflammatory cells in sputum were assessed in 12 patients with mild, 14 with moderate and 12 with severe persistent asthma, as well as in 13 control subjects. Asthmatic patients were categorized into those with eosinophilic or non-eosinophilic airway inflammation. Sputum PGE(2), cysLT and 8-isoprostane, and urinary LTE(4) were extracted on immunoaffinity sorbents, and the concentrations of all mediators were measured using enzyme immunoassays. Sputum nitrate concentrations were measured on a chemiluminescence analyzer. Sputum PGE(2) concentrations were higher in both moderate (1710 pg/mL) and severe asthmatic (1590 pg/mL) compared with control subjects (827 pg/mL) (P<0.05). CysLT concentrations were higher in moderate asthmatic compared with control or severe asthmatic subjects (P<0.05). Sputum PGE(2) concentrations were lower in patients with eosinophilic (1180 pg/mL) compared with non-eosinophilic airway inflammation (2520 pg/mL) (P=0.02). In contrast, sputum cysLT and urinary LTE(4) concentrations were higher in those with eosinophilic airway inflammation (P<0.05). Forced expiratory volume in 1 s was inversely correlated with sputum eosinophils in all asthmatic patients (r(s)=-0.5, P=0.002). There were no significant differences in sputum 8-isoprostane or nitrate concentrations. Increased airway concentrations of PGE(2) are consistent with the hypothesis that PGE(2) has a bronchoprotective and anti-inflammatory role in patients with more severe asthma. A reduced PGE(2) to cysLT ratio in the airways may adversely affect lung function and contribute to persistence of symptoms and airway remodelling in patients with eosinophilic airway inflammation.

Dividing the FEV1 into its component parts

LETTERS TO THE EDITORDividing the FEV1 into its component partsPeter T. Macklem, and Charles G. IrvinPeter T. Macklem, and Charles G. IrvinPublished Online:01 Jul 2008https://doi.org/10.1152/japplphysiol.90489.2008MoreSectionsPDF (29 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: Sorkness et al. (1) show that the forced expiratory volume in 1 s (FEV1) expressed as percent predicted can be broken down into its two components, forced vital capacity (FVC) and FEV1/FVC, also expressed as percent predicted. They claim that “this is a novel approach [for partitioning the FEV1] in a quantitative manner”. In fact, this quantitative novelty was introduced 12 years ago by Gibbons et al. (2) for exactly the same reason that Sorkness et al. (1) use it: to detect asthmatic subjects with severe disease. Sorkness et al. suggest that severe asthmatic subjects may be fundamentally different from nonsevere asthmatic subjects in that they have airway closure, causing gas trapping, and this can be detected by a lower FVC in the severe group. If so, the frequency distribution of fall in FVC at the dose of agonist producing a 20% decline in FEV1 (PC20) should be bimodal. However, Gibbons et al. (2) found that in 146 asthmatic subjects, this distribution was unimodal and normally distributed. It could be claimed that the numbers were insufficient to demonstrate bimodality, but 64 of the 146 patients had a fall in FVC ≥ 15%, accounting for 75% or more of the fall in FEV1.Curiously, in a control group of only 20 healthy subjects receiving high-dose methacholine challenge, there was clear evidence of bimodality: 16 subjects had a fall in FVC ranging from 0 to 15% and there were none between 15 and 19.9% but 4 between 20 and 55%. Could it be that these four subjects were at risk for developing asthma?Sorkness et al. (1) did not report the fall in FVC at the PC20, and their subjects were preselected as either severe or nonsevere asthma. This selection would prevent detection of bimodality; an unselected group of patients like those studied by Gibbons et al. (2) would be required. Sorkness et al. (1) claim that their study “is the first … to show the predilection of severe asthma for air trapping over the entire range of airflow limitation,” but the asthmatic subjects studied by Gibbons et al. had a mean baseline value of FVC and FEV1 of 105.7% and 98.9% predicted, respectively, with lower 95% confidence limits of 76.9% and 70.1% predicted, respectively, so the claim of Sorkness et al. to originality can be challenged. Finally, Gibbons et al. found no correlation between PC20 and percent fall in FVC at the PC20, proving that sensitivity to methacholine and response to the agonist are unrelated phenomena.REFERENCES1 Sorkness RL, Bleeker ER, Busse WW, Calhoun WJ, Castro M, Chung KF, Curran-Everett D, Erzurum SC, Gaston BM, Israel E, Jarjour NN, Moore WC, Peters SP, Teague WG, Wenzel SE, for the National Hearth, Lung, and Blood Institute Severe Asthma Research Program. Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation. J Appl Physiol 104: 394–403, 2008.Link | ISI | Google Scholar2 Gibbons WJ, Sharma A, Lougheed D, Macklem PT. Detection of excessive bronchoconstriction in asthma. Am J Respir Crit Care Med 153: 582–589, 1996.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: P. T. Macklem, P. O. Box 250, Lansdowne, Ontario, Canada K0E 1L0 (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByReply to Macklem and IrvinRonald L. Sorkness1 July 2008 | Journal of Applied Physiology, Vol. 105, No. 1 More from this issue > Volume 105Issue 1July 2008Pages 392-392 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.90489.2008PubMed18641234History Published online 1 July 2008 Published in print 1 July 2008 Metrics

Expression of the proapoptotic protein Bax is reduced in bronchial mucous cells of asthmatic subjects.

The present studies were designed to determine whether our findings in mice showing that the Bcl-2-associated protein X (Bax), which plays a role in the resolution of allergen-induced mucous cell metaplasia, can be applied to asthma in humans. Immunostaining of autopsy tissues from mild and severe asthmatic subjects showed a significant reduction in the percentage of Bax-positive mucous cells compared with those from nonasthmatic controls. To exclude the possibility that postmortem changes may have affected Bax expression, Bax mRNA levels in airway epithelial cells obtained from nonsmoking asthmatic subjects were compared with those from nonasthmatic controls. Because the number of cells obtained by bronchial brushings is limited, we developed a robust preamplification procedure of cDNA before quantitative real-time PCR to allow detection of 100 gene targets from limited sample size, even when it was prepared from partially degraded RNA. cDNA was prepared by reverse transcription from RNA isolated from bronchial epithelial cells obtained by bronchial brushings from well-characterized subjects without lung disease and from subjects with mild asthma. Quantitative analysis showed that Bax mRNA levels were significantly reduced in samples obtained from asthma patients compared with nonasthma controls. Furthermore, Bax mRNA levels were reduced when primary airway epithelial cells from 10 individuals were treated in culture with the T helper 2 cytokine IL-13. These studies show that Bax expression is reduced in airway epithelial cells of even mild asthmatic subjects and suggest that restoring Bax expression may provide a clinical approach for restoring the normal numbers of epithelial cells and reduced mucous hypersecretion in asthma.

Factors Associated with Severe Disease in a Population of Asthmatic Children of Bogota, Colombia

Background. There is evidence that prevalence and severity of asthma in children has risen. Risk factors for severe asthma have been studied extensively in children living in developed countries, but little is known about factors determining the severity of asthma in Latin American countries. The aim of this study was to investigate the role of suspected, potential risk factors for asthma severity in a population of children living in urban Bogota. Methods. We studied 175 children, 2 to 16 years old, with asthma attending an asthma clinic. Severe cases and nonsevere asthmatic subjects were compared regarding suspected, potential pre-, peri-, and postnatal risk factors. Results. After controlling for asthma duration, we found that children never breast fed (OR, 11.53; 95% CI, 2.35–56.50; p = 0.003), mothers 30 years or younger at the child's birth (OR, 3.44; 95% CI, 1.23–9.63; p = 0.019), usual use of acetaminophen for fever in the child in the 12 months previous to the survey application (OR, 3.13; 95% CI, 1.14–8.56; p = 0.026), older siblings at birth (OR, 3.81; 95% CI, 1.28–11.32; p = 0.016), and primary or secondary school as the highest level of education attained by mother (OR, 3.20; 95% CI, 1.01–10.07; p = 0.046) were all independent predictors of severe asthma. Conclusion. No breastfeeding, maternal age at child's birth of less than 30 years, routine use of acetaminophen for fever in the child in the 12 months previous to the survey application, older siblings at birth, and primary or secondary school as the highest level of education attained by mother were independent predictors of severe asthma. Some of these risk factors are clearly modifiable. Further prospective, population-based studies with a bigger sample size and a more representative sample of the general population residing in the city are needed to retest and clarify these associations.

Airway nitric oxide release is reduced after PBS inhalation in asthma

Exhaled nitric oxide (NO) is elevated in asthma, but the underlying mechanisms remain poorly understood. Recent results in subjects with asthma have reported a decrease in exhaled breath pH and ammonia, as well as altered expression and activity of glutaminase in both alveolar and airway epithelial cells. This suggests that pH-dependent nitrite conversion to NO may be a source of exhaled NO in the asthmatic airway epithelium. However, the anatomic location (i.e., airway or alveolar region) of this pH-dependent NO release has not been investigated and could impact potential therapeutic strategies. We quantified airway (proximal) and alveolar (peripheral) contributions to exhaled NO at baseline and then after PBS inhalation in stable (mild-intermittent to severe) asthmatic subjects (20-44 yr old; n = 9) and healthy controls (22-41 yr old; n = 6). The mean (SD) maximum airway wall flux (pl/s) and alveolar concentration (ppb) at baseline in asthma subjects and healthy controls was 2,530 (2,572) and 5.42 (7.31) and 1,703 (1,567) and 1.88 (1.29), respectively. Compared with baseline, there is a significant decrease in the airway wall flux of NO in asthma as early as 15 min and continuing for up to 60 min (maximum -28% at 45 min) after PBS inhalation without alteration of alveolar concentration. Healthy control subjects did not display any changes in exhaled NO. We conclude that elevated airway NO at baseline in asthma is reduced by inhaled PBS. Thus airway NO may be, in part, due to nitrite conversion to NO and is consistent with airway pH dysregulation in asthma.

Targeting tumour necrosis factor-α in corticosteroid-dependent asthma

Asthma is a chronic inflammatory disease of the airways characterised by bronchospasm attacks triggered by various stimuli. The underlying pathogenic mechanism is eosinophil-dominated inflammation causing bronchial hyper-responsiveness, but in more severe asthma subjects, neutrophil cells and their directly related cytokines, such as TNF-α, are known to play a role in the inflammatory process and also in diminished corticosteroid sensitivity. The bronchospasm attacks are usually relieved by short-acting β2-agonists, whereas maintenance therapy is represented mainly by inhaled corticosteroids. However, in severe persistent asthma or in difficult to treat asthma these can be ineffective even at high doses. Therefore, other therapeutic alternatives are needed, and etanercept, a TNF-α-blocking agent, could represent one of them provided the safety and efficacy data are supportive.

Is the upregulation of bradykinin B2 receptors by TGF-β1 one of the missing pieces in the “airway hyperresponsiveness” puzzle?

transforming growth factor (TGF)-β1 belongs to the TGF-β family of proteins corresponding to a set of pleiotropic secreted signaling molecules with unique and potent immunoregulatory properties ([10][1]). TGF-β1 is produced by every leukocyte lineage, including lymphocytes, macrophages, and

Characterization of two polymorphisms in the leukotriene C 4 synthase gene in an Australian population of subjects with mild, moderate, and severe asthma

Background The cysteinyl-leukotrienes (cys-LTs) are proinflammatory mediators that are important in the pathophysiology of asthma. LTC 4 synthase is a key enzyme in the cys-LT biosynthetic pathway, and studies in small populations have suggested that a promoter polymorphism (A -444C) in the gene might be associated with asthma severity and aspirin intolerance. Objective We sought to screen the LTC 4 synthase gene for polymorphisms and to determine whether there is an association between these polymorphisms and asthma severity or aspirin sensitivity in a large, well-phenotyped population and to determine whether this polymorphism is functionally relevant. Methods The coding regions of the LTC 4 synthase gene were screened for polymorphisms and the A -444C polymorphism was analyzed in a large Australian white adult population of mild (n = 282), moderate (n = 236), and severe asthmatic subjects (n = 86) and nonasthmatic subjects (n = 458), as well as in aspirin-intolerant asthmatic subjects (n = 67). The functional activity of the promoter polymorphism was investigated by transient transfection of HL-60 cells with a promoter construct. Results A new polymorphism was identified in intron 1 of the gene (IVS1-10c>a) but was not associated with asthma. Association studies showed that the A -444C polymorphism was weakly associated with asthma per se, but there was no association between the C -444 allele and chronic asthma severity or aspirin intolerance. A meta-analysis of all the genetic studies conducted to date found significant between-study heterogeneity in C -444 allele frequencies within different clinical subgroups. In vitro functional studies showed no significant differences in transcription efficiency between constructs containing the A -444 allele or the C -444 allele. Conclusions Our data confirm that, independent of transcriptional activity, the C -444 allele in the LTC 4 synthase gene is weakly associated with the asthma phenotype, but it is not related to disease severity or aspirin intolerance.

Evaluation of basal and dynamic measures of adrenocortical activity with high dose inhaled fluticasone in asthmatic and healthy subjects

Rationale We evaluated the human corticotrophin releasing factor (hCRF) stimulated plasma cortisol response to fluticasone propionate (FP) 2000μg daily in severe asthmatic and healthy subjects. Methods 10 severe asthmatic and 10 healthy subjects received FP 2000μg daily via a 750ml primed spacer for 2 weeks. Patients stopped their usual inhaled corticosteroid therapy during a 1-week washout period prior to FP treatment and for the duration of the study. Measurements including plasma cortisol pre and post hCRF stimulation, and overnight 10-hour urinary cortisol excretion corrected for creatinine (OUCC) were made at baseline following washout and at 12 hours following the last dose of FP. Results Baseline values prior to FP were not significantly different comparing asthmatic vs. healthy subjects for pre hCRF plasma cortisol (p=0.54), post hCRF plasma cortisol (p=0.92), and OUCC (p=0.30). Comparing values at baseline vs. post FP, there was no significant suppression of either pre: 378.2 vs. 357.4 nmol/l (p=0.37) or post: 510.5 vs. 507.9 nmol/l (p=0.90) hCRF plasma cortisol and OUCC: 8.2 vs. 7.5 nmol/mmol (p=0.38) in asthmatic patients. In healthy subjects, all outcomes were significantly suppressed for baseline vs. post FP; pre hCRF plasma cortisol: 423.5 vs. 200.2 nmol/l (p=0.002), post hCRF plasma cortisol: 503.5 vs. 291.1 nmol/l (p=0.001) and OUCC: 6.5 vs. 2.4 nmol/mmol (p=0.002). Conclusion Severe persistent asthmatics are protected from the systemic adverse effects of high dose FP, as assessed by basal and dynamic measures of hypothalamic-pituitary-adrenal axis activity.

Reduced eosinophil apoptosis in induced sputum correlates with asthma severity.

This study was carried out to investigate the relationship between induced sputum eosinophil apoptosis and clinical severity score, airway obstruction and symptom scores in patients with chronic stable asthma. Altogether, 41 chronic stable asthmatic subjects of varying severity defined by Aas score and 17 control subjects underwent spirometry, symptom questionnaire and successful sputum induction. Sputum was processed and cytospins prepared for light microscopy to determine normal and apoptotic eosinophils. Mild asthmatic subjects had a significantly lower percentage sputum eosinophils and a significantly higher eosinophil apoptotic ratio (AR) than moderate or chronic severe asthmatics. Severe asthmatic subjects had a significantly greater age, duration of asthma and sputum eosinophil count x mL(-1) than mild asthmatic subjects. Asthmatic subjects' symptom scores, severity scores and age inversely correlated with AR and the percentage of sputum eosinophils. Baseline forced expiratory volume in one second inversely correlated with percentage sputum eosinophils and positively correlated with AR. The study demonstrates a relationship between reduced sputum eosinophil apoptosis and increased clinical severity of chronic stable asthma, providing additional evidence that eosinophil apoptosis may be important in the resolution of eosinophilic airway inflammation in asthma.

Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects.

The role of nitric oxide (NO) needs to be further clarified in allergic inflammation. This study was designed to investigate the relationships between NO metabolites and eosinophil count, eosinophil cationic protein (ECP), interleukin (IL)-5 in induced sputum from asthmatics. Hypertonic saline-induced sputum was obtained in 25 asthmatic subjects, among which 13 patients were examined before and after anti-asthmatic medications including steroid preparations. Ten normal subjects were enrolled as controls. Fresh expectorated sputum separated from saliva was treated with equal volume of dithiothreitol 0.1%, cytospinned for cell count, and the supernatant was collected for biochemical assay. NO metabolites were assayed by using modified Griess reaction. ECP was measured by fluoroimmunoassay, and detected IL-5 by a sandwich ELISA. Asthmatic subjects, compared with controls, had significantly higher concentration of NO metabolites (1035.4 +/- 125.3 vs 557.2 +/- 101.5 micromol/L, P < 0.01), higher percentage of eosinophils (25.6 +/- 4.6 vs 1.7 +/- 0.2%, P < 0.01), and higher levels of ECP (1117.8 +/- 213.9 vs 154.6 +/- 47.4 microg/L, P < 0.01) in the induced sputum. IL-5 was detected more frequently in asthmatic subjects than in control subjects (11/25 [44%] vs 1/10 [10%], P < 0.05). According to asthma severity, moderate to severe asthmatic subjects (n = 18) had higher level of NO metabolites (1143.8 +/- 156.3 vs 575.5 +/- 89.5 micromol/L, P < 0. 01), higher levels of ECP and IL-5 (P < 0.01, respectively) in the induced sputum than in those of mild asthmatic subjects (n = 7). NO metabolites, the percentage of eosinophils, the levels of ECP, and IL-5 were reduced following treatment with anti-asthmatic drugs (P < 0.01, respectively). There were significant positive correlations between NO metabolites and percentage of eosinophils or ECP (r = 0. 34, P < 0.05; r = 0.28, P < 0.05). Negative correlations were noted between FEV1, FEV1/FVC and proportion of eosinophils, ECP, or IL-5 levels. These findings confirmed that the level of NO metabolites was increased in the tracheobronchial secretion of asthmatic subjects and was paralleled with severity of asthma. Measurement of NO metabolites in induced sputum may be used for monitoring the degree of airway inflammation in asthmatics.

Case-control study of salmeterol and near-fatal attacks of asthma.

BACKGROUND: A case-control study was undertaken to investigate the hypothesis that the use of the long acting beta agonist salmeterol increases the risk of a near-fatal attack of asthma. METHODS:...

Effects of airway calibre on lung delivery of nebulised salbutamol.

BACKGROUND: A study was undertaken to test the hypothesis that airway calibre may alter lung deposition and therefore lung bioavailability of inhaled drugs as a result of narrowed airways reducing...

Cytokine expression in normal, atopic, and asthmatic subjects using the combination of sputum induction and the polymerase chain reaction.

The importance of cytokines in the asthmatic inflammatory response is becoming apparent. The aim of this study was to determine whether the non-invasive method of induced sputum combined with the polymerase chain reaction would allow the detection of messenger RNA (mRNA) encoding a range of cytokines on a qualitative basis. Four groups were studied comprising 10 normal subjects, six atopic, 10 mild and five moderately severe asthmatic subjects. Sputum was induced by the inhalation of nebulised 3.5% saline and total RNA extracted from the expectorated cells. Expression of cytokine message within induced sputum was examined by reverse transcription and the polymerase chain reaction (PCR) using primers specific for a range of cytokines (IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, RANTES, TNF alpha, IFN alpha, IFN gamma). Presence or absence of the signal was determined at 35 and 70 cycles of PCR by electrophoretic size fractionation on ethidium bromide stained agarose gels. Cytokine message was detectable in sputum by this method. All samples showed a positive result for actin control. Analysis of signal for the cytokines in all subjects showed that, at 70 cycles, IL-1, IL-5, IL-8, and TNF alpha were detected in more subjects than would be expected by chance. IL-5 mRNA was detected in more of the asthmatic patients (moderate 80%, mild 40%) than in the atopic subjects (33%), who in turn showed expression of this cytokine in more individuals than nonatopic subjects (10%). The combination of sputum induction and PCR appears to be a useful, non-invasive tool to explore the chronic inflammation of asthma and possibly other lung disorders. It should enable differences between normal and asthmatic subjects to be identified for future confirmation by quantitative techniques.

Cardiac role in exercise limitation in asthmatic subjects with special reference to disease severity

We wanted to assess limitations in cardiorespiratory fitness of asthmatic subjects, acclimatized to 1,300 m altitude and in a clinically stable state. We therefore studied 16 young asthmatic and 8 normal young subjects during an incremental bicycle exercise test. The asthmatics were divided into two groups, according to the Aas classification: a moderate asthma group (degree 2 and 3, no pulmonary impairment during symptom-free intervals), and a severe asthma group (degree 4 and 5, with persistent airway obstruction). The results showed that cardiorespiratory fitness is limited in severe asthmatic subjects acclimatized to an altitude of 1,300 m, due to decreased cardiac output and stroke volume. At submaximal exercise, the lower stroke volume is compensated by an increased arteriovenous oxygen content difference, but this compensation no longer exists at maximal exercise, which explains the lower maximal oxygen uptake in the severe asthma group. The hypothesis that the high tidal volume in the severe asthma group could lead to a decrease in left ventricular performance is considered. In conclusion, with respect to cardiorespiratory response to exercise, asthmatics should not be considered as a homogeneous group. Furthermore, relationship between ventilatory requirement and its consequences upon cardiac stroke volume provides a strong argument for the physical rehabilitation of asthmatics. Indeed, aerobic training can decrease the ventilation level for a given workload, and thus reduce inappropriate adaptations to exercise.

Regional deposition of 3.6-micron particles and lung function in asthmatic subjects

In a group of moderately severe asthmatic subjects, regional deposition of 3.6-microns (aerodynamic diameter) monodispersed Teflon particles labeled with 111In was studied twice. The particles were inhaled with maximally deep inhalation at 0.5 l/s. Lung retention was measured at 0, 6, 24, and 48 h by use of a profile scanner equipped with two 13 x 5-cm NaI crystals. The retentions at 24 (Ret24) and 48 h were highly correlated (r = 0.96 with a slope of the regression line close to 1). There was a poor correlation between retention at 6 h and Ret24 (r = 0.54). The Ret24 values at the two exposures were well correlated (r = 0.86). There were significant correlations between airway resistance as well as single-breath nitrogen test phase III and Ret24 (r = 0.70 and 0.67, respectively). The correlation between single-breath nitrogen test phase III and Ret24 persisted also when only subjects within a narrow interval of airway resistance were included. The study indicates that regional deposition can be studied by measurements of Ret24 in subjects with moderately severe asthma and that it is dependent on changes in both large and small airways.