Bioecological aspects of triatomines and marsupials as wild Trypanosoma cruzi reservoirs in urban, peri-urban and rural areas in the Western Brazilian Amazon.

In the Amazon region, Trypanosoma cruzi transmission cycles involve a great diversity of Triatominae vectors and mammal reservoirs. Some Rhodnius spp. mainly inhabit palm trees that act as microhabitats for hosts and vectors. The current study aimed to describe aspects of the bio-ecology of the vectors and reservoirs of T. cruzi in relation to human populations resident near areas with large quantities of palm trees, in rural, peri-urban and urban collection environments, located in the Western Brazilian Amazon. Rhodnius pictipes and Didelphis marsupialis were respectively the most predominant vector and reservoir, with rates of 71% for R. pictipes and 96.5% for D. marsupialis. The vast majority of T. cruzi isolates clustered with TcI. The most prevalent haplotype was TcI COII1 (69.7%). Mauritia flexuosa and Attalea phalerata were the main ecological indicators of infestation by triatomines. Birds were the most common food source (27,71%). T. cruzi isolated from R. robustus has the haplotype HUM-13, previously detected in a chronic Chagas patient living in the same area. Our results demonstrate the relevance of this study, with the occurrence of elevated infection rates in animals, and suggest the importance of the Amazon zones where there is a risk of infection in humans.

Physiological strain to prolonged exercise bouts at the walk-run transition speeds depends on locomotion mode in healthy untrained men.

This study compared the physiological strain induced by prolonged walking and running performed at the walk-run transition speed (WRTS) in healthy untrained men. Twenty volunteers (age: 28 ± 5.01 years; height: 174.0 ± 0.3 cm; body mass: 74.5 ± 0.6 kg) underwent the following: (a) ramp-incremental maximal cardiopulmonary exercise test (CPET); (b) specific protocol to detect the WRTS; and (c) two 30-min walking and running bouts at WRTS (mean ± SD: 6.9 ± 0.06 km/h). Expired gases were collected during exercise bouts via the metabolic cart. A significant effect of locomotion mode (F = 4.8, P < 0.001) was observed with running resulting in higher cardiorespiratory responses than walking at the WRTS (oxygen uptake: mean difference = 0.26 L/min; pulmonary ventilation: mean difference = 5.53 L/min; carbon dioxide output: mean difference = 0.32 L/min; heart rate: mean difference = 13 beats/min; total energy expenditure: mean difference = 59 kcal). The rating of perceived exertion was similar across locomotion modes (mean difference = 0.3; P = 0.490). In conclusion, running promoted greater cardiorespiratory responses than walking at the WRTS in untrained healthy men. These data might have practical impact on aerobic training performed at intensities corresponding to WRTS.

The relationship between biomarkers of fungal allergy and lung damage in asthma.

BACKGROUND: Immunological biomarkers are the key to the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) and fungal sensitisation, but how these relate to clinically relevant outcomes is unclear. OBJECTIVES: To assess how fungal immunological biomarkers are related to fixed airflow obstruction and radiological abnormalities in moderate to severe asthma. METHODS: Cross-sectional study of 431 asthmatics. Inflammatory biomarkers, lung function and an IgE fungal panel to colonising filamentous fungi, yeasts and fungal aeroallergens were measured. CT scans were scored for the presence of radiological abnormalities. Factor analysis informed the variables used in a k-means cluster analysis. Fixed airflow obstruction and radiological abnormalities were then mapped to these immunological variables in the cluster analysis. RESULTS: 329 (76.3%) subjects were sensitised to ≥ 1 fungi. Sensitisation to Aspergillus fumigatus and/or Penicillium chrysogenum was associated with a lower post-bronchodilator FEV1 compared with those not sensitised to fungi ((73.0 (95% CI 70.2-76) vs. 82.8 (95% CI 78.5-87.2)% predicted, P < 0.001), independent of atopic status (P = 0.005)), and an increased frequency of bronchiectasis (54.5%, P < 0.001), tree-in-bud (18.7%, P < 0.001) and collapse/consolidation (37.5%, P = 0.002). Cluster analysis identified three clusters: (i) hypereosinophilic (n = 71, 16.5%), (ii) high immunological biomarker load and high frequency of radiological abnormalities (n = 34, 7.9%) and (iii) low levels of fungal immunological biomarkers (n = 326, 75.6%). CONCLUSIONS AND CLINICAL RELEVANCE: IgE sensitisation to thermotolerant filamentous fungi, in particular A. fumigatus but not total IgE, is associated with fixed airflow obstruction and a number of radiological abnormalities in moderate to severe asthma. All patients with IgE sensitisation to A. fumigatus are at risk of lung damage irrespective of whether they meet the criteria for ABPA.

Hemodynamic Responses and Perceived Exertion During Continuous and Discontinuous Resistance Exercise.

This study compared acute responses of systolic and diastolic blood pressure (SBP/DBP), cardiac output (Q), heart rate (HR), stroke volume (SV), total peripheral resistance (TPR) and rate of perceived exertion (RPE) during resistance exercise performed continuously and discontinuously. Hemodynamic responses and RPE were assessed in the last of 4 sets of 12 repetitions of the knee extension with load corresponding to 70% of 12 repetition maximum, performed continuously (C) or discontinuously, with pauses of 5 s (D5) or 10 s (D10) interspersed in the middle of sets. The increase in SBP was higher for D10 (34.0±8.4%) and D5 (34.1±13.2%) vs. C (19.8±10.3%; P<0.001), while no difference was detected for DBP. Q (P=0.03) and SV (P=0.02) were higher, but HR was lower (P=0.04) in discontinuous vs. continuous. TPR remained stable during continuous, but significant decreases occurred during the pauses in the discontinuous protocols (P<0.001). The BP was higher in discontinuous than in continuous protocols, but the RPE was attenuated in discontinuous compared to continuous exercise. In conclusion, hemodynamic responses were exacerbated during resistance exercise performed discontinuously, but the perceived exertion was lowered.

Spectral analyses of systolic blood pressure and heart rate variability and their association with cognitive performance in elderly hypertensive subjects.

Systolic hypertension is associated with cognitive decline in the elderly. Altered blood pressure (BP) variability is a possible mechanism of reduced cognitive performance in elderly hypertensives. We hypothesized that altered beat-to-beat systolic BP variability is associated with reduced global cognitive performance in elderly hypertensive subjects. In exploratory analyses, we also studied the correlation between diverse discrete cognitive domains and indices of systolic BP and heart rate variability. Disproving our initial hypothesis, we have shown that hypertension and low education, but not indices of systolic BP and heart rate variability, were independent predictors of lower global cognitive performance. However, exploratory analyses showed that the systolic BP variability in semi-upright position was an independent predictor of matrix reasoning (B = 0.08 ± .03, P-value = 0.005), whereas heart rate variability in semi-upright position was an independent predictor of the executive function score (B = -6.36 ± 2.55, P-value = 0.02). We conclude that myogenic vascular and sympathetic modulation of systolic BP do not contribute to reduced global cognitive performance in treated hypertensive subjects. Nevertheless, our results suggest that both systolic BP and heart rate variability might be associated with modulation of frontal lobe cognitive domains, such as executive function and matrix reasoning.

Disruption of redox homeostasis and brain damage caused in vivo by methylmalonic acid and ammonia in cerebral cortex and striatum of developing rats.

Hyperammonemia is a common finding in children with methylmalonic acidemia and propionic acidemia, but its contribution to the development of the neurological symptoms in the affected patients is poorly known. Considering that methylmalonic acid (MMA) and propionic acid (PA) predominantly accumulate in these disorders, we investigated the effects of hyperammonemia induced by urease treatment in 30-day-old rats receiving an intracerebroventricular (ICV) injection of MMA or PA on important parameters of redox homeostasis in cerebral cortex and striatum. We evaluated glutathione (GSH) concentrations, sulfhydryl content, nitrate and nitrite concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, and the activity of antioxidant enzymes. MMA decreased GSH concentrations and sulfhydryl content and increased nitrate and nitrite concentrations in cerebral cortex and striatum from hyperammonemic rats, whereas MMA or ammonia per se did not alter these parameters. MMA plus hyperammonemia also decreased glutathione reductase activity in rat cerebral cortex, but did not affect catalase, superoxide dismutase and glutathione peroxidase activities, neither DCFH oxidation. Furthermore, ICV PA administration alone or combined with hyperammonemia did not alter any of the evaluated parameters. We also found that pre-treatment with antioxidants prevented GSH reduction and sulfhydryl oxidation, whereas N(ω)-nitro-L-arginine methyl ester (L-NAME) prevented the increased nitrate and nitrite concentrations provoked by MMA plus ammonia treatments. Histological alterations, including vacuolization, ischemic neurons, and pericellular edema, were observed in brain of hyperammonemic rats injected with MMA. The data indicate a synergistic effect of MMA and ammonia disturbing redox homeostasis and causing morphological brain abnormalities in rat brain.

Work volume in strength training is not affected by rest interval strategy.

AIM: Between-set rest intervals (RI) may be determined using exercise-recovery-ratio (ERR) or fixed periods. The study investigated the influence of different ERR and fixed RI on the training volume in sessions aiming for hypertrophy with upper-body exercises recruiting different muscle mass (bench press-BP and triceps extension-TE). METHODS: Sixteen men (25±2 years, 78±6 kg, 178±5 cm) with previous experience in resistance training performed 5 sets of maximum repetitions in each exercise with five RI protocols (RR1:3 [I3]; ERR1:5 [I5]; ERR1:7 [I7]; increasing ERR [IP] (1:3-1:5-1:7-1:9); 2-min fixed [2F]) in a counterbalanced design. The number of repetitions and work volume (load x repetitions) in each set and along the sessions (load x repetitions x sets) were compared across the RI protocols. RESULTS: The maximum repetitions decreased along with the sets in both exercises, but TE had lower percent decrease compared to BP, due to a longer time to perform the sets and therefore longer absolute rest time (P<0.05). The I3 exhibited the lowest repetitions sustainability (P<0.05). The training volume in I7, IP and 2F was always higher than I3 and I5 (P>0.05). However the absolute RI in 2F (~2 min) was shorter than in I7 and IP (~3 min), which reduced the total duration of the training session. CONCLUSION: Determining between-set RI based on ERR instead of using fixed intervals does not enable more work to be done in multiple-set/high intensity resistance training sessions.

Isolation of Aspergillus fumigatus from sputum is associated with elevated airborne levels in homes of patients with asthma.

Indoor bioaerosols, such as mold spores, have been associated with respiratory symptoms in patients with asthma; however, dose-response relationships and guidelines on acceptable levels are lacking. Furthermore, a causal link between mold exposure and respiratory infections or asthma remains to be established. The aim of this study was to determine indoor concentrations of Aspergillus fumigatus and a subset of clinically relevant fungi in homes of people with asthma, in relation to markers of airways colonization and sensitization. Air and dust samples were collected from the living room of 58 properties. Fungal concentrations were quantified using mold-specific quantitative PCR and compared with traditional microscopic analysis of air samples. Isolation of A. fumigatus from sputum was associated with higher airborne concentrations of the fungus in patient homes (P = 0.04), and a similar trend was shown with Aspergillus/Penicillium-type concentrations analyzed by microscopy (P = 0.058). No association was found between airborne levels of A. fumigatus and sensitization to this fungus, or dustborne levels of A. fumigatus and either isolation from sputum or sensitization. The results of this study suggest that the home environment should be considered as a potential source of fungal exposure, and elevated home levels may predispose people with asthma to airways colonization.

Isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator FEV1.

BACKGROUND: Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown. OBJECTIVE: To provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease. METHODS: We recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis. RESULTS: Forty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus (P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV (1) (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, (P < 0.01). CONCLUSION AND CLINICAL RELEVANCE: Numerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV (1) , which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common.

Aerobic exercise intensity influences hypotension following concurrent exercise sessions.

The study investigated whether resistance and aerobic concurrent exercise (CE) with different intensities influenced postexercise hypotension (PEH). 21 healthy men (20.7±0.7 yr) performed 4 sessions: control [CTL 60 min of rest], and CE1, CE2, and CE3 consisting respectively of 2 sets of 6 exercises at 80% 1RM followed by 30 min of cycle ergometer exercise at 50%, 65%, and 80% of peak oxygen consumption (VO2peak). All sessions lasted approximately 60 min and began with resistance prior to aerobic sessions. Systolic (SBP) and diastolic (DBP) blood pressure (BP) were assessed at baseline and every 10 min during 120-min recovery. The magnitude of SBP decrease was similar after all CE sessions [CE1: 4.2±2.5 mmHg; CE2: 4.8±2.7 mmHg; CE3: 6.0±2.0 mmHg; p=0.06], but the PEH lasted approximately 1 h longer following CE2 and CE3 [120 min] compared to CE1 [60-70 min] (P<0.05). The magnitude of DBP decrease was slightly greater after CE3 and CE2 [2 mmHg] than after CE1 [1 mmHg] (P<0.05), being longer following CE3 [60 min] compared to CE2 and CE1 [40 min] (P<0.05). In conclusion, CE sessions combining resistance and aerobic sessions elicited PEH, especially when the intensity of the aerobic exercise was higher than 65% VO2peak.

Influence of cardiopulmonary exercise testing protocol and resting VO(2) assessment on %HR(max), %HRR, %VO(2max) and %VO(2)R relationships.

The findings of previous studies investigating the strength of the relationships between the percentages of maximal heart rate (%HR(max)), heart rate reserve (%HRR), maximal oxygen uptake (%VO(2max)), and oxygen uptake reserve (%VO(2)R) have been equivocal. This inconsistency between studies could largely be due to differences in methodology. The purpose of this study was therefore to determine whether different VO(2max) test protocols and resting VO(2) assessment influence the relationships between the %HR(max), %HRR, %VO(2max), and %VO(2)R. Thirty-three young men performed maximal treadmill protocols (ramp, Bruce) to assess HR(max) and VO(2max). Resting VO(2) was assessed as follows: a) resting VO(2standard), using strict criteria (24 h exercise abstention, alcohol, soft drinks, or caffeine; 8 h fasting; 30 min assessment); b) resting VO(2sitting) and; c) resting VO(2standing) (both 5 min before exercise testing). The %HRR was closer to %VO(2max) than to %VO(2)R, especially in the ramp protocol (p<0.001). In the Bruce protocol, relationships were closer to the identity line, and there was no significant difference between %HRR and %VO(2max), or %VO(2)R. The VO(2max) was significantly higher in the ramp protocol compared to the Bruce protocol (p<0.001). In both protocols resting VO(2) assessment produced no significant difference in the intercepts and slopes of the %HRR-%VO(2)R relationships obtained from individual regression models. The %VO(2)R calculated using resting VO(2standard) was closer to %HRR compared to VO(2sitting) and VO(2standing). The premise that %HRR is more strongly related to %VO(2)R than to %VO(2max) was not confirmed. Methodological differences should be considered when interpreting previous studies investigating %HR(max), %HRR, %VO(2max), and %VO(2)R relationships.

Walk-run transition in young and older adults: with special reference to the cardio-respiratory responses.

Cardio-respiratory responses of young and older subjects performing walking and running protocols at the walk-run transition speed (WRT) were compared. A total of 26 volunteers assigned to younger (YG, 24 +/- 3 years) and older (OG, 64 +/- 6 years) groups underwent a protocol to determine the WRT used in 6-min walking and running protocols. Oxygen uptake (VO(2)), ventilation (V (E)), expired carbon dioxide (VCO(2)), heart rate (HR) and perceived exertion (RPE) were assessed. Oxygen pulse (O(2) pulse) and respiratory exchange ratio (RER) were calculated. The WRT was not different between groups (OG: 6.84 +/- 0.69 km h(-1) vs. YG: 7.04 +/- 0.77 km h(-1), P = 0.62). No between-group differences were found within a given gait pattern for VO(2) (P = 0.061) and VCO(2) (P = 0.076). However, VO(2) (P = 0.0022) and VCO(2) (P = 0.0041) increased in OG when running, remaining stable in YG (VO(2): P = 0.622; VCO(2): P = 0.412). The VE was higher in OG compared to YG in walking (P = 0.030) and running (P = 0.004) protocols. No age-related (P = 0.180) or locomotion (P = 0.407) effects were found for RER. The HR increased in OG and between-group difference was detected while running (P = 0.003). No within- (P = 0.447) or between-group (P = 0.851) difference was found for O(2) pulse. The net VO(2) increased from walking to running in OG (P < 0.0001) but not in YG (P = 0.53), while RPE was lower in YG (P = 0.041) but stable in OG (P = 0.654). In conclusion, the WRT speed was similar across the age groups. However, the VO(2) and VCO(2) increase from walking to running was larger for OG than YG. The HR, VE and RPE were also higher when running in OG compared to YG. Therefore, the locomotion strategy had different impacts on the metabolic demand of older and younger subjects.

Sputum IL-5 concentration is associated with a sputum eosinophilia and attenuated by corticosteroid therapy in COPD.

BACKGROUND: Airway inflammation in chronic obstructive pulmonary disease (COPD) is predominately neutrophilic, but some subjects demonstrate eosinophilic airway inflammation. Whether these inflammatory phenotypes have differential cytokine and chemokine expression is unknown. OBJECTIVES: To assess the sputum concentrations of cytokines and chemokines and their response to oral corticosteroid therapy in COPD subjects with or without a sputum eosinophilia. METHODS: Cytokine and chemokine concentrations were measured using the meso-scale device platform. To assess validity, recovery of exogenous spikes was examined. The concentrations of the validated mediators were measured in COPD sputum from subjects with or without a sputum eosinophilia. In a subgroup with a sputum eosinophilia, the response to oral prednisolone 10 mg for 1 month was examined. RESULTS: The recovery in sputum of exogenous spiked mediators was >80% in 11/26 cytokines and chemokines. In supernatants from eosinophilic (n = 39) versus non-eosinophilic (n = 59) sputa, the geometric mean (95% CI) concentration was increased for IL-5 [9.0 (4.5-18) pg/ml vs. 3.6 (2.7-6.3) pg/ml, p = 0.03]. IL-5 alone was correlated with sputum eosinophil counts (r = 0.33, p = 0.001), and was attenuated following treatment with prednisolone [n = 9; mean difference 2.3 pg/ml (0.2-4.3), p = 0.032]. CONCLUSION: We have validated the use of the meso-scale device platform for cytokine and chemokine measurements in the sputum supernatants in COPD. Sputum IL-5 was associated with a sputum eosinophilia and was attenuated following oral corticosteroid therapy. Whether this cytokine is important in the pathogenesis of COPD in a subgroup of patients warrants further investigation.

Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial.

Evidence suggests that eosinophilic airway inflammation is important in the pathogenesis of severe chronic obstructive pulmonary disease (COPD) exacerbations. The present authors tested the hypothesis that a management strategy that aims to reduce sputum eosinophil counts is associated with a reduction in exacerbations of COPD. A total of 82 patients with COPD were randomised into two groups. One group was treated according to traditional guidelines (British Thoracic Society (BTS) group) and the other (sputum group) was treated with the additional aim of minimising eosinophilic airway inflammation, assessed using the induced sputum eosinophil count. The primary outcome was exacerbations, which were categorised as mild, moderate or severe. The frequency of severe exacerbations per patient per year was 0.5 and 0.2 in the BTS and sputum groups, respectively (mean reduction 62%). The majority of this benefit was confined to patients with eosinophilic airway inflammation. There was no difference in the frequency of mild and moderate exacerbations. The average daily dose of inhaled or oral corticosteroids during the trial did not differ between the groups. Out of 42 patients in the sputum group, 17 required regular oral corticosteroids to minimise eosinophilic airway inflammation. A management strategy that aims to minimise eosinophilic airway inflammation, as well as symptoms, is associated with a reduction in severe exacerbations of chronic obstructive pulmonary disease.

Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease.

BACKGROUND: An association between the sputum eosinophil count and the response to a 2 week course of prednisolone has previously been reported in patients with chronic obstructive pulmonary disease (COPD). Whether the response to inhaled corticosteroids is related to the presence of eosinophilic inflammation is unclear. METHODS: A randomised, double blind, crossover trial of placebo and mometasone furoate (800 microg/day), each given for 6 weeks with a 4 week washout period, was performed in subjects with COPD treated with bronchodilator therapy only. Spirometric tests, symptom scores, chronic respiratory disease questionnaire (CRQ), and induced sputum were performed before and after each treatment phase. RESULTS: Ninety five patients were recruited of which 60 were randomised. Overall there were no treatment associated changes in forced expiratory volume in 1 second (FEV(1)), total CRQ, or sputum characteristics. After stratification into tertiles by baseline eosinophil count, the net improvement in post-bronchodilator FEV(1) increased with mometasone compared with placebo progressively from the least to the most eosinophilic tertile. The mean change in post-bronchodilator FEV(1) with mometasone compared with placebo in the highest tertile was 0.11 l (95% CI 0.03 to 0.19). This improvement was not associated with a fall in the sputum eosinophil count. CONCLUSIONS: An increased sputum eosinophil count is related to an improvement in post-bronchodilator FEV(1) following treatment with inhaled mometasone in COPD, but the improvement is not associated with a reduction in the sputum eosinophil count.

Airway function and markers of airway inflammation in patients with treated hypothyroidism.

BACKGROUND: There is increasing evidence of an association between organ specific autoimmune diseases, particularly autoimmune thyroid disease and respiratory morbidity. A study was undertaken to determine whether patients with autoimmune thyroid disease have objective evidence of airway inflammation and dysfunction. METHODS: Twenty six non-smoking women with treated hypothyroidism and 19 non-smoking controls completed a symptom questionnaire and underwent full lung function tests, capsaicin cough reflex sensitivity measurement, methacholine challenge test, and sputum induction over two visits. RESULTS: Symptoms of cough (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p = 0.04) were reported more commonly in patients than controls. Patients with hypothyroidism had heightened cough reflex sensitivity compared with controls (geometric mean concentration of capsaicin causing five coughs: 40 v 108 mmol/l; mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to 2.5; p = 0.008) and a significantly higher proportion of patients had airway hyperresponsiveness (methacholine provocative concentration (PC(20)) <8 mg/ml: 38% v 0%; p = 0.016). Patients with hypothyroidism also had a significantly higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p = 0.048). CONCLUSION: Patients with treated hypothyroidism report more respiratory symptoms and have objective evidence of airway dysfunction and inflammation.

Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: Some patients with chronic obstructive pulmonary disease (COPD) respond to corticosteroid therapy. Whether these patients have different airway pathology from other COPD patients is unclear. We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation. METHODS: We did a randomised, double-blind, crossover trial. Patients who had COPD treated with bronchodilators only were assigned placebo and 30 mg prednisolone daily for 2 weeks each, in a random order, separated by a 4-week washout period. Before and after each treatment period, we assessed patients with spirometry, symptom scores, the chronic respiratory disease questionnaire (CRQ), incremental shuttle walk test, and induced sputum. Analysis was done by intention to treat. FINDINGS: 83 patients were recruited, of whom 67 were randomised. The geometric mean sputum eosinophil count fell significantly after prednisolone (from 2.4% to 0.4%; mean difference six-fold [95% CI 3.1-11.4]) but not after placebo. Other sputum cell counts did not change. After stratification into tertiles by baseline eosinophil count, postbronchodilator forced expiratory volume in 1 s (FEV1) and total scores on the CRQ improved progressively after prednisolone from the lowest to the highest eosinophilic tertile, compared with placebo. The mean change in postbronchodilator FEV1, total CRQ score, and shuttle walk distance with prednisolone compared with placebo in the highest tertile was 0.19 L (0.06-0.32), 0.62 (0.31-0.93), and 20 m (5-35), respectively. INTERPRETATION: Our findings suggest that eosinophilic airway inflammation contributes to airflow obstruction and symptoms in some patients with COPD and that the short-term effects of prednisolone are due to modification of this feature of the inflammatory response. The possibility that sputum eosinophilia identifies a subgroup of patients who particularly respond to long-term treatment with inhaled corticosteroids should be investigated.

Six-year follow-up after exposure and clomipramine therapy for obsessive compulsive disorder.

To determine whether gains from exposure therapy are lasting in patients with chronic obsessive compulsive disorder, the authors followed up 34 (85%) of 40 such patients who had been treated 6 years earlier with exposure therapy for 3 or 6 weeks and with clomipramine or placebo for 36 weeks. Severity of obsessive compulsive disorder was assessed by rating the discomfort caused by the time devoted to four target rituals, the Behavioral Avoidance Test, and the Compulsion Checklist. Mood was assessed by the 17-item Hamilton Rating Scale for Depression, the Wakefield Self-Assessment Depression Inventory, and the Anxiety scale. In addition, the patients' general adjustment was assessed. The authors found that the group as a whole remained significantly improved on obsessive compulsive symptoms, work and social adjustment, and depression; however, the group returned to pretreatment levels (slight to moderate) of general anxiety. They found that neither clomipramine nor placebo affected long-term outcome and that the majority of patients who were taking clomipramine or other antidepressants at follow-up were no more improved that those who were not taking antidepressants. Better long-term outcome correlated with more exposure therapy (6 weeks of therapy vs. 3 weeks) and with better compliance with the exposure therapy homework. The best predictor of long-term outcome was improvement at the end of treatment. Subjects who had initially been most depressed were more likely to receive psychotropic medication during follow-up. Initial severity of illness did not preclude benefit from exposure therapy.