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PubMed2004

Coparenting, family-level processes, and peer outcomes: the moderating role of vagal tone.

This article examines the relationship between coparenting and family-level processes during preschool and peer relationship outcomes in middle childhood, and the hypothesis that children's ability to regulate emotion (as indexed by basal vagal tone and the ability to suppress vagal tone) may moderate this relationship. We predicted that high vagal tone and a greater ability to suppress vagal tone would buffer children from the effects of negative coparenting and family processes. Results indicated that hostile-withdrawn coparenting predicted higher levels of conflicted play and lower levels of positive peer conversation. Vagal suppression also moderated the relationship between hostile-withdrawn coparenting and peer conflict. For children who were unable to suppress vagal tone, hostile-withdrawn coparenting was associated with higher levels of peer conflict, while for children who were able to suppress vagal tone there was no relationship hostile-withdrawn coparenting and peer conflict. The relationship between hostile-withdrawn coparenting and positive peer conversation was also moderated by children's ability to suppress vagal tone. For children who were unable to suppress vagal tone, there was no relationship between hostile-withdrawn coparenting and positive peer conversation, while for those who were able to suppress vagal tone, hostile-withdrawn coparenting was associated with less positive peer conversation. Cohesive family-level processes also predicted positive conversation in play at age 9 after controlling for positive conversation at age 5; however, this relationship was not moderated by vagal suppression. Basal vagal tone also did not function as a moderator of relations between hostile-withdrawn coparenting and peer play. Results are discussed in terms of the effects of negative coparenting on children with different patterns of modulating physiological arousal.

Child↗

PubMed2001

Cognitive and neurobehavioral functioning after mild versus moderate traumatic brain injury in older adults.

This study evaluated the early cognitive and neurobehavioral outcomes of older adults with mild versus moderate traumatic brain injury (TBI). Thirty-five patients who were age 50 years and older and sustained mild or moderate TBI were prospectively recruited from acute care hospitals. Patients were administered cognitive and neurobehavioral measures up to 2 months post-injury. Demographically comparable control participants received the same measures. Patients and controls did not have previous histories of substance abuse, neuropsychiatric disturbance, dementia, or neurologic illness. Moderate TBI patients performed significantly poorer than mild TBI patients and controls on most cognitive measures, whereas the mild patients performed comparably to controls. In contrast, both mild and moderate patients exhibited significantly greater depression and anxiety/somatic concern than controls. The results indicate that the classification of TBI as mild versus moderate is prognostically meaningful as applied to older adults. The findings extend previous investigations in young adults by demonstrating a relatively good cognitive outcome on objective measures, but subjective complaints after a single, uncomplicated mild TBI in older persons.

Aged↗

PubMed2003

Effects of daily, light and moderate-heavy ethanol exposure on extent of hepatic injury and recovery following toxin-induced acute hepatitis in rats.

Daily, light ethanol consumption enhances hepatic regeneration following 70% partial hepatectomy in rats. Whether such consumption has a beneficial effect on the outcome following toxin-induced acute hepatitis has yet to be determined. One hundred ten adult male Spragne-Dawlay rats (200-250 g) were randomized to receive daily gavages with ethanol 1.0 g/kg (light ethanol group), 3.0 g/kg (moderate-heavy ethanol group), or an equal volume of tap water (controls). On day 30, a single injection of D-galactosamine hydrochloride (1.0 g/kg) (D-gal), a potent hepatotoxin that induces liver failure within 24-48 hr, was administered intraperitoneally. Gavages were discontinued and rats killed (N = 4-6/group) on days 1, 3, 5, 7, and 10 after D-gal. Serum AST, bilirubin, and liver histology served to document the extent of liver injury and [3H] thymidine incorporation into hepatic DNA: hepatic regenerative activity. Compared to controls, peak serum AST levels were significantly decreased in the light (-40%, P < 0.05) and increased in the moderate-heavy (+32%, P < 0.05) ethanol groups. Serum bilirubin levels approximately doubled in the light ethanol group while increasing sixfold in the moderate-heavy and control groups (P < 0.05). Histologic evidence of hepatic injury (graded 0-IV) was limited in the light ethanol group, intermediate in controls, and most extensive in the moderate-heavy ethanol group (P < 0.05). Despite less hepatic injury, hepatic regeneration was similar in the light ethanol group compared to controls and significantly impaired in the moderate-heavy ethanol group (P < 0.01). In conclusion, the results of this study indicate that daily, light ethanol administration attenuates hepatic injury, improves hepatic function, and enhances hepatic regeneration following toxin-induced hepatitis in rats.

Animals↗

PubMed1994

Social-cognitive processes of severely violent, moderately aggressive, and nonaggressive boys.

This study examined social-cognitive processes of aggressive and nonaggressive boys at preadolescent and early adolescent age levels. The social-cognitive variables included processing of cues, attributions, social problem solving, affect labeling, outcome expectations, and perceived competence and self-worth. Results indicated that a wide range of social-cognitive processes is distorted and deficient for violent and moderately aggressive children, and that different types of social cognition contribute unique variance in discriminating among groups. Severely violent boys at both age levels had difficulties with cue recall, attributions, social problem solving, general self-worth, and a pattern of endorsing unusually positive affects that they may experience in different settings. Moderately aggressive boys shared some of the social-cognitive difficulties demonstrated by severely violent boys, but they also displayed indications that their aggression may be more planfully aimed to achieve expected outcomes. When the moderately aggressive and the violent boys differed from the nonaggressive boys on attributional biases and low perceived self-worth, a continuum existed with violent boys displaying more extreme social-cognitive dysfunctions than the moderately aggressive boys. These findings carry implications for cognitive-behavioral intervention with severely violent and moderately aggressive youths.

Adolescent↗

PubMed1986

The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations.

In this article, we attempt to distinguish between the properties of moderator and mediator variables at a number of levels. First, we seek to make theorists and researchers aware of the importance of not using the terms moderator and mediator interchangeably by carefully elaborating, both conceptually and strategically, the many ways in which moderators and mediators differ. We then go beyond this largely pedagogical function and delineate the conceptual and strategic implications of making use of such distinctions with regard to a wide range of phenomena, including control and stress, attitudes, and personality traits. We also provide a specific compendium of analytic procedures appropriate for making the most effective use of the moderator and mediator distinction, both separately and in terms of a broader causal system that includes both moderators and mediators.

Attitude↗

PubMed2003

Which treatment for whom for ADHD? Moderators of treatment response in the MTA.

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.

Attention Deficit Disorder with Hyperactivity↗

PubMed1982

Reduced plasma concentration of 1,25-dihydroxyvitamin D in children with moderate renal insufficiency.

We measured the plasma concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) in 39 children comprising three groups; eight with moderate renal insufficiency (GFR of 25 to 50 ml/min/1.73 M2, seven of whom had tubulointerstitial disease), eight with severe renal insufficiency (on chronic hemodialysis), and 23 healthy control subjects. The mean plasma concentration of 1,25-(OH)2D was reduced by some 40% (P less than 0.002) in the children with moderate renal insufficiency, and by some 80% (P less than 0.001) in the children with severe renal insufficiency. In the children with moderate renal insufficiency, the reduced concentration of 1,25-(OH)2D was associated with increased serum concentrations of immunoreactive parathyroid hormone (iPTH) and reduced serum concentrations of 1,25-(OH)2D was associated with increased serum concentrations of immunoreactive parathyroid hormone (iPTH) and reduced serum concentrations of calcium and phosphorus. When analyzed over the range of renal function from normal through severely impaired, values of iPTH correlate inversely and significantly with those of 1,25-(OH)2D. Growth was impaired in four of the eight children with moderate renal insufficiency. The results of the current study suggest that in children with moderate renal insufficiency, a reduction in the renal synthesis and in the plasma concentration of 1,25-(OH)2D may be important pathogenetic events in disordered metabolism of calcium and phosphorus, including secondary hyperparathyroidism.

Adolescent↗

PubMed1997

Enhanced natriuretic response to neutral endopeptidase inhibition in patients with moderate chronic renal failure.

Atrial natriuretic factor (ANF) has natriuretic, renin-suppressing and chronic hypotensive actions that may be utilized by inhibition of ANF degradation by neutral endopeptidase, E.C.24.11 (NEP). Three groups of 8 male patients [GFR 103 +/- 8 (Normal), 64 +/- 6 (Moderate CRF), and 16 +/- 2 ml/min (Severe CRF)] received 100 mg i.v. bolus of the NEP inhibitor candoxatrilat or placebo in random order in a double-blind crossover study. GFR (51CR-EDTA), ERPF (125I-hippuran). ANF (IRMA), urinary cGMP (RIA) and albumin (RIA) and sodium excretion and flow rate were measured hourly for two hours before and for seven hours after candoxatrilat administration. After candoxatrilat plasma ANF rose two- to threefold from baseline, and remained elevated for 5(N) and 7(M,S) hours (P < 0.01(N,S), P < 0.03(M)) associated with an immediate rise in urine cGMP excretion from 23.5(N), 25.4(M) and 10.4(S) nmol/hr (base) to 51.7(N), 73.8(M) and 27.5(S)(peak) lasting 7(N,M,S) hours (P < 0.01(N,M,S)). There was a marked natriuresis in all three groups, the cumulative sodium excretion at seven hours post-candoxatrilat being 104(N), 140(M), 102(S) mmol (P < 0.05(N,M,S)). This was greatest in those with moderate CRF (moderate CRF vs. normal, P = 0.036, moderate vs. severe CRF, P = 0.01, normal vs. severe CRF, P = 0.74). Following candoxatrilat there was a near doubling of the urine flow rate (P < 0.01(N,S), P < 0.02(M)). Urine albumin excretion increased in patients with renal failure (P < 0.01), but there was no change in GFR, ERPF or systemic blood pressure. We conclude that the marked natriuretic effects of acute NEP inhibition seen in normal subjects are enhanced in the presence of moderate CRF and sustained even in severe renal impairment.

Adult↗

PubMed2006

Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy.

The role of dexamethasone to reduce delayed emesis following highly emetogenic chemotherapy is proven, but there is less evidence of benefit after mild-moderately emetogenic regimens. Here, we develop and evaluate a Dexamethasone Symptom Questionnaire (DSQ) to assess the side effects of dexamethasone in the week after patients receive moderately emetogenic chemotherapy. The DSQ was first optimised with the aid of a focus group. Sixty patients receiving oral dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy for cancer completed and then evaluated the DSQ. Patients reported that the DSQ was clearly worded and addressed items important to them. Patients receiving dexamethasone reported moderate-severe problems with insomnia (45%), indigestion/epigastric discomfort (27%), agitation (27%), increased appetite (19%), weight gain (16%) and acne (15%) in the week following chemotherapy. The side effects of dexamethasone may outweigh its benefits when used with moderately emetogenic chemotherapy. A randomised, double-blind crossover trial is underway to determine the effect of dexamethasone on nausea and vomiting, and the impact of side effects of dexamethasone and of nausea and vomiting on quality of life.

Acne Vulgaris↗

PubMed1997

The effects of long-term, moderate intensity, intermittent exercise on aerobic capacity, body composition, blood lipids, insulin and glucose in overweight females.

OBJECTIVE: To test the hypotheses that the accumulation of 30 min of moderate intensity, intermittent exercise, 5d/week-1, for 32 weeks, will increase aerobic capacity, alter body composition and improve blood lipids, insulin and glucose. Secondly, to identify individuals who may respond to moderate intensity, intermittent exercise. SUBJECTS: Thirteen sedentary, moderately obese females, aged 43 +/- 11 (y), body mass index (BMI) 32.7 +/- 7.7 (kg/M2), body fat 40.6 +/- 8.8 (%), VO2max 24.0 +/- 4.6 (ml/kg-1/min-1). MEASUREMENTS: Aerobic capacity, body composition, blood lipids, fasting insulin and glucose, energy intake. RESULTS: Group data showed no significant changes for aerobic capacity, body composition, blood lipids, insulin or glucose. However, 7 of the 13 subjects increased aerobic capacity, lost fat weight and improved insulin. Adherence to the exercise regimen was excellent with 82.6 +/- 10.0% of the exercise completed. CONCLUSIONS: Moderate intensity, intermittent exercise for a total of 30 min, 5d/week,-1 for 32 weeks duration, was not a sufficient stimulus to significantly increase aerobic capacity, and alter weight, body composition or improve blood lipids, insulin or glucose for the entire group. However, those subjects who increased aerobic capacity and decreased fat weight were significantly older, had lower maximal aerobic capacity and greater body fat at baseline compared to the six subjects who did not increase aerobic capacity and decrease fat weight. For both groups, moderate intensity, intermittent exercise showed excellent adherence and this may be a useful model for future research studies.

Adult↗

PubMed2003

Moderate physical activity permits acute coupling between serum leptin and appetite-satiety measures in obese women.

OBJECTIVES: To investigate whether moderate physical activity or snack intake influence appetite sensations and subsequent food intake in obese women. Associations between serum leptin and appetite ratings were also investigated. METHODS: In all, 10 obese women (mean age+/-s.d.: 50.0+/-8.5 y; mean body mass index (BMI)+/-s.d.: 37.2+/-6.5 kg m(-2)) were submitted in random order to three trials: Moderate physical activity (20 min brisk walking), Snack (58.5 g chocolate-based) and Control (sitting, TV-watching). Appetite and satiety were assessed by visual analogue scales, and serum leptin, blood glucose and plasma free fatty acids were measured at baseline, pre- and postintervention and 1 h postintervention (ie, before dinner). A buffet-style dinner was provided subsequent to the three trials. RESULTS: The moderate physical activity and snack intake both produced lower appetite and higher satiety and fullness perceptions, compared to control, following the intervention. No significant differences were found in subsequent food intake. Serum leptin concentrations did not differ between trials. Serum leptin was not associated with appetite or satiety sensations at any time during the control or the snack trials, but was correlated following moderate physical activity (prospective food consumption r(s)=-0.83, P=0.003; hunger r(s)=-0.79, P=0.007; desire to eat r(s)=-0.69, P=0.02; satiety r(s)=0.71, P=0.02; fullness r(s)=0.66, P=0.04). These associations were not influenced by BMI or fat mass. CONCLUSIONS: Moderate physical activity and snack intake suppress the appetite of obese women acutely. The associations between circulating leptin and appetite-satiety ratings suggest leptin involvement in short-term appetite regulation in response to physical activity-induced factors.

Adult↗

PubMed1995

Acute exercise effects on urinary losses and serum concentrations of copper and zinc of moderately trained and untrained men consuming a controlled diet.

Acute exercise effect on urinary losses and serum concentrations of Cu and Zn of eight moderately trained and five untrained male runners were determined to ascertain effects of training on trace metal responses owing to acute exercise. Maximum oxygen uptake (VO2 max) of the moderately trained subjects was 47.3 +/- 2.3 and that of the untrained subjects was 34.7 +/- 1.9 ml kg-1 min-1. Subjects consumed a controlled diet to minimize changes due to dietary intake. Immediately following acute exercise at 90% of VO2 max to exhaustion (30 s exercise and 30 s rest periods), serum Zn and Cu levels of moderately trained and untrained subjects were elevated. Serum Zn of moderately trained subjects 2 h post-exercise was lower than before exercise (13.5 +/- 0.05 versus 12.5 +/- 0.05 mumol 1-1, a similar trend was observed for untrained subjects. Serum concentrations of both groups were similar to pre-exercise levels 2 h post-exercise. Changes in urinary losses of Zn and Cu, associated with the acute strenuous exercise of short duration employed in this study, were not significantly different. These data demonstrate that increases in serum Cu and Zn following acute exercise are independent of training status for moderately trained and untrained men.

Copper↗

PubMed2002

Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection.

Although excessive alcohol consumption in combination with hepatitis C virus (HCV) infection is known to increase the risk of liver cirrhosis, the effect of moderate alcohol intake remains to be elucidated. The aim of this study was to evaluate the effect of moderate alcohol consumption on fibrosis progression in HCV infection. A group of 78 patients with HCV infection and moderate alcohol consumption were analysed retrospectively. All patients had undergone two liver biopsies, with a median time between biopsies of 6.3 years, and had not received any antiviral therapy. Their lifetime drinking history was recorded. All patients except one had daily alcohol consumption below 40 g of ethanol (median 4.8 g/day, interquartile range 1.1-11.6 g/day) during the period between the biopsies. The patients whose liver fibrosis had deteriorated had a higher total alcohol consumption and higher drinking frequency between the biopsies. The degree of fibrosis progression was greater in patients with a total alcohol intake and drinking frequency above the median level for the group. A multiple logistic regression analysis showed that drinking frequency and time between biopsies were independently associated with fibrosis progression. Hence, even moderate alcohol intake seems to increase fibrosis progression in HCV-infected patients. From that point of view, total abstention ought to be recommended. If this is not achieved, occasional use of alcohol is probably less harmful than daily drinking for patients with low or moderate alcohol consumption.

Adult↗

PubMed2002

Intestinal energy metabolism after ischemia-reperfusion: Effects of moderate hypothermia and perfluorocarbons.

PURPOSE: This study investigated the roles of moderate hypothermia and extraluminal oxygenated perfluorcarbon (PFC) on intestinal metabolism after ischemia-reperfusion. METHODS: A model of 30-minute intestinal ischemia followed by 60 minutes of reperfusion was used. The animals were maintained at either normothermia (36.5 to 37.5 degrees C) or moderate hypothermia (31 to 32 degrees C). Four groups of adult rats were studied (n = 8 per group): (A) sham at normothermia, (B) ischemia-reperfusion at normothermia, (C) ischemia-reperfusion at hypothermia and, (D) ischemia-reperfusion with extraluminal oxygenated PFC perfusion during ischemia at normothermia. Intestinal phosphocreatine, ATP and lactate levels were measured. Histologic changes in the intestine were evaluated. RESULTS: Intestinal ischemia-reperfusion at normothermia caused a marked reduction in phosphocreatine and ATP with an increase in lactate. Moderate hypothermia exerted beneficial effects by attenuating the depletion of high-energy phosphates and the elevation of lactate. Extraluminal PFC perfusion during ischemia failed to produce a protective effect on high-energy phosphates, although it reduced lactate accumulation. Moderate hypothermia significantly decreased the degree of mucosal damage. CONCLUSIONS: Whole-body moderate hypothermia protects the small intestine from reperfusion injury as measured both biochemically and histologically. Extraluminal oxygenated PFC administration during ischemia did not protect the intestine from reperfusion injury in this model.

Adenosine Triphosphate↗

PubMed2005

Oxygen uptake kinetics during moderate and heavy intensity exercise in humans: the influence of hypoxia and training status.

This study examined the influence of moderate hypoxia on the oxygen uptake (V.O(2)) kinetic response (primary time constant and slow component amplitude) during moderate and heavy cycle exercise in twenty-seven male subjects with various training status. Nine endurance trained (21.5 +/- 2.6 yr), nine sprint trained (22.9 +/- 5.7 yr), and nine untrained controls (24.0 +/- 4.4 yr) completed incremental tests to exhaustion in normoxia (inspired gas concentration or FIO (2) = 21 % O(2)) and hypoxia (FIO (2) = 13 % O(2)) to establish the FIO (2)-specific ventilatory threshold (VT) and maximal VO(2). Subsequently, the subjects performed repeated constant work rate cycling exercises during 7 min at moderate intensity (80 % of FIO (2)-specific VT) and heavy intensity (midway between the FIO (2) specific VT and maximal VO(2)). Pulmonary gas exchange was measured breath-by-breath during all exercise sessions. For both moderate and heavy intensities, the time constant of the primary VO(2) component was significantly (p < 0.05) slowed by approximately 25 to 30 % in hypoxia compared to normoxia to the same extent in the three groups. Hypoxia produced a more important decrease in the amplitude of the slow component in endurance athletes (- 36 %) than in sprinters (- 30 %) and controls (- 12 %). These results suggest that both primary and slow components of VO(2) kinetics during the adjustment to moderate- and heavy-intensity exercise are sensitive to hypoxia while training status tended to modulate partly the slow component amplitude.

Adult↗

PubMed2001

Subjects with mild and moderate asthma respond to segmental allergen challenge with similar, reproducible, allergen-specific inflammation.

BACKGROUND: The relationship between severity of asthma and bronchial inflammation is poorly understood. OBJECTIVE: We examined acute and subacute inflammatory responses to allergen in subjects with mild and moderate persistent asthma to evaluate whether different cellular and mediator responses to endobronchial allergen challenge are associated with differences in disease severity. METHODS: Segmental allergen challenge was performed in 8 subjects with mild and 10 subjects with moderate allergic asthma to compare baseline airways inflammation and allergen-induced inflammatory responses 24 hours later. This evaluation was repeated after 6 weeks in 9 subjects to investigate the reproducibility of these inflammatory responses. RESULTS: Subjects with mild and moderate asthma had similar decreases in FEV(1) in response to segmental allergen challenge (9.1% +/- 4.2% vs 15.1% +/- 4.6%, P = .35). There was no difference in inflammatory cell counts or cytokine concentrations in the groups with mild and moderate asthma at baseline or after saline or allergen challenge. Repeat segmental allergen challenge 6 weeks later showed that these cellular and cytokine responses were reproducible. CONCLUSION: Segmental allergen challenge in subjects with mild and moderate asthma produces similar allergen-specific physiologic and inflammatory responses that are reproducible 6 weeks later. In this model of allergic asthma, acute responses to allergen do not appear to be related to disease severity.

Adult↗

PubMed2002

Differential roles of IL-16 and CD28/B7 costimulation in the generation of T-lymphocyte chemotactic activity in the bronchial mucosa of mild and moderate asthmatic individuals.

BACKGROUND: IL-16 is an important T-cell chemotactic cytokine in asthmatic airways; its release from allergen-stimulated bronchial mucosa in mild asthma has been shown to be dependent on CD28/B7 costimulation. OBJECTIVE: We have extended our previous studies to investigate the role of IL-16 and CD28/B7 costimulation in T-lymphocyte chemotactic activity (TLCA) released from the bronchial mucosa in more severe asthma. METHODS: TLCA was determined in the supernatants of induced sputum and allergen-stimulated bronchial mucosal explants from healthy volunteers and volunteers with mild and moderately severe asthma by means of a Boyden chamber technique. The contribution of IL-16 to the activity was evaluated through use of a neutralizing monoclonal antibody; the contribution of CD28/B7 costimulation to allergen-induced release of TLCA was determined through use of CTLA4-Ig fusion protein and neutralizing monoclonal antibodies to CD80 (B7.1) and CD86 (B7.2). RESULTS: Induced sputum and unstimulated explants from asthmatic subjects generated significant spontaneous TLCA (P <.05). Both mild and moderate asthmatic explants showed significantly elevated Dermatophagoides pteronyssinus -induced release of TLCA, but only in mild asthma could sputum and allergen-stimulated explant TLCA be inhibited by anti-IL-16 (median inhibition, 39% and 59%; P <.05). In addition, allergen released significant quantities of IL-16 from mild asthmatic explants (P <.05) but not from moderate asthmatic explants. Antibodies to the CD28 counter-ligands CD80 and CD86 inhibited allergen-induced release of TLCA in mild asthmatic explants by 94% (P <.05) and 62%, but TLCA release from moderate asthmatic explants was unaffected by CTLA4-Ig. CONCLUSION: These results show that TLCA release in moderate asthmatic airways, in contrast to mild asthmatic airways, is not dependent on CD28/B7 costimulation and does not involve IL-16.

Abatacept↗

PubMed2003

Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression.

BACKGROUND: Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta, IL-11, and IL-17 are profibrotic cytokines involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in those with severe disease. OBJECTIVE: The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition. METHODS: We used immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and collagen types I and III in the airways of patients with mild asthma (n = 9), patients with moderate-to-severe asthma (n = 10), and control subjects without asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups. In addition, repeat biopsies were obtained in the patients with moderate-to-severe asthma after a 2-week course of oral corticosteroids. RESULTS: TGF-beta expression was significantly higher in all groups with asthma, and it did not decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17 were increased in patients with moderate-to-severe asthma compared with patients with mild asthma and normal controls (P <.05). The expression of these cytokines decreased with oral corticosteroids in the moderate-to-severe group to levels that were comparable to those seen in the patients with mild asthma and in the normal controls (P <.005). Expression of types I and III collagens was higher in the patients with moderate-to-severe asthma than in the patients with mild asthma and the controls (P <.05; P <.001). Treatment with corticosteroids did not decrease the expression of types I and III collagens. CONCLUSIONS: These results confirm the association of increased levels of TGF-beta, IL-11, IL-17, and types I and III collagens with severe disease and suggest that the failure of cortico-steroids to decrease collagen deposition might be due to persistently elevated TGF-beta expression.

Administration, Oral↗