Effects of Chronic Exposure to Air Pollution from Sao Paulo City on Coronary of Swiss Mice, from Birth to Adulthood

To explore the hypothesis that air pollution promotes cardiovascular changes, Swiss mice were continuously exposed, since birth, in two open-top chambers (filtered and nonfiltered for airborne particles <= 0.3 mu m) placed 20 m from a street with heavy traffic in downtown Sao Paulo, twenty-four hours per day for four months. Fine particle (PM(2.5)) concentration was determined gravimetrically; hearts were analyzed by morphometry. There was a reduction of the PM(2.5) inside the filtered chamber (filtered = 8.61 +/- 0.79 mu g/m(3), nonfiltered = 18.05 +/- 1.25 mu g/m(3), p < .001). Coronary arteries showed no evidence of luminal narrowing in the exposed group but presented higher collagen content in the adventitia of LV large-sized and RV midsized vessels (p = .001) and elastic fibers in both tunicae adventitia and intima-media of almost all sized arterioles from both ventricles (p = .03 and p = .001, respectively). We concluded that chronic exposure to urban air since birth induces mild but significant vascular structural alterations in normal individuals, presented as coronary arteriolar fibrosis and elastosis. These results might contribute to altered vascular response and ischemic events in the adulthood.

Centrilobular Fibrosis: An Underrecognized Pattern in Systemic Sclerosis

Background: The impressive association of lung involvement and gastroesophageal reflux in scleroderma raises the possibility of a cause-effect relationship. Objectives: To determine clinical, radiological and histopathological features of systemic sclerosis (SSc) patients according the presence or absence of centrilobular fibrosis (CLF). Methods: Twenty-eight SSc patients with lung involvement were submitted to open lung biopsy and the specimens classified for the presence of CLF (bronchocentric distribution of the lesions and intraluminal matter according to the classification of idiopathic interstitial pneumonia). HRCT, pulmonary function tests and esophageal analysis were also performed. Subsequently, cyclophosphamide was introduced for the nonspecific interstitial pneumonia subgroup and antireflux treatment was intensified for isolated CLF patients. Results: Isolated CLF was found in 21% of the biopsies and also found associated to nonspecific interstitial pneumonia in 84% of these patients. The other 3 cases had usual interstitial pneumonia, pulmonary hypertension and respiratory bronchiolitis-associated interstitial lung disease. The histopathological analysis revealed that all 6 patients with isolated CLF had the bronchocentric distribution and intraluminal basophilic content, with foreign bodies detected in one third of them. The central distribution of lung involvement on HRCT was found in 67% of these patients with a consistent patchy distribution (100%). Ground glass (67%) and consolidation (33%) were the predominant patterns found. The constant clinical finding in all isolated CLF cases was dyspnea, esophageal abnormalities and a moderate lung impairment (FVC: 63.83 +/- 16.31%; DLCO: 61.66 +/- 18.84%). Lung function parameters in isolated CLF patients remained stable after 1 year of exclusively intensive antireflux treatment (FVC, p = 0.23; DLCO, p = 0.59). Conclusions: The novel description of CLF pattern in SSc lung disease with peculiar histological, tomographic and clinical features will certainly contribute to a more appropriate therapeutic approach. Copyright (C) 2008 S. Karger AG, Basel

Influence of respiratory biofeedback associated to re-expansive ventilation patterns in individuals with functional mouth breathing

Objectives: Assess the effect of re-expansive respiratory patterns associated to respiratory biofeedback (RBF) on pulmonary function, respiratory muscle strength and habits in individuals with functional mouth breathing (FMB). Methods: Sixty children with FMB were divided into experimental and control groups. The experimental group was submitted to 15 sessions of re-expansive respiratory patterns associated to RBF (biofeedback pletsmovent; MICROHARD (R) V1.0), which provided biofeedback of the thoracic and abdominal movements. The control group was submitted to 15 sessions using biofeedback alone. Spirometry, maximum static respiratory pressure measurements and questions regarding habits (answered by parents/guardians) were carried out before and after therapy. The Student`s t-test for paired data and non-parametric tests were employed for statistical analysis at a 5% Level of significance. Results: Significant changes were found in forced vital. capacity, Tiffeneau index scores, maximum expiratory pressure, maximum inspiratory pressure and habits assessed in FMB with the use of RBF associated to the re-expansive patterns. No significant differences were found comparing the experimental and control groups. Conclusions: The results allow the conclusion that RBF associated to re-expansive patterns improves forced vital capacity, Tiffeneau index scores, respiratory muscle strength and habits in FMB and can therefore be used as a form of therapy for such individuals. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Patterns of viral load in chronic hepatitis B patients in Brazil and their association with ALT levels and HBeAg status

Serum hepatitis B virus (HBV) DNA [eve[ is a predictor of the development of cirrhosis and hepatocellullar carcinoma in chronic hepatitis B patients. Nevertheless, the distribution of viral load levels in chronic HBV patients in Brazil has yet to be described. This cross-sectional study included 564 participants selected in nine Brazilian cities located in four of the five regions of the country using the database of a medical diagnostics company. Admission criteria included hepatitis B surface antigen seropositivity, availability of HBV viral toad samples and age >= 18 years. Mates comprised 64.5% of the study population. Mean age was 43.7 years. Most individuals (62.1%) were seronegative for the hepatitis B e antigen (HBeAg). Median serum ALT level was 34 U/L. In 58.5% of the patients HBV-DNA levels ranged from 300 to 99,999 copies/mL; however, in 21.6% levels were undetectable. Median HBV-DNA level was 2,351 copies/mL. Over 60% of the patients who tested negative for HBeAg and in whom ALT level was less than 1.5 times the upper limit of the normal range had HBV-DNA levels > 2,000 IU/mL, which has been considered a cut-off point for indicating a liver biopsy and/or treatment. In conclusion, HBV-DNA level identified a significant proportion of Brazilian individuals with chronic hepatitis B at risk of disease progression. Furthermore, this tool. enables those individuals with high HBV-DNA levels who are susceptible to disease progression to be identified among patients with normal or stightly elevated ALT.

Impact of number of vessels disease on outcome of patients with stable coronary artery disease: 5-year follow-up of the medical, angioplasty, and bypass surgery study (MASS)

Objective: To evaluate whether the number of vessels disease has an impact on clinical outcomes as well as on therapeutic results accordingly to medical, percutaneous, or surgery treatment in chronic coronary artery disease. Methods: We evaluated 825 individuals enrolled in MASS study, a randomized study to compare treatment options for single or multivessel coronary artery disease with preserved left ventricular function, prospectively followed during 5 years. The incidence of overall mortality and the composite end-point of death, myocardial infarction, and refractory angina were compared in three groups: single vessel disease (SVD n = 214), two-vessel disease (2VD n = 253) and three-vessel disease (3VD n = 358). The relationship between baseline variables and the composite end-point was assessed using a Cox proportional hazards survival model. Results: Most baseline characteristics were similar among groups, except age (younger in SVD and older in 3VD, p < 0.001), lower incidence of hypertension in SVD (p < 0.0001), and lower levels of total and LDL-cholesterol in 3VD (p = 0.004 and p = 0.005, respectively). There were no statistical differences in composite end-point in 5 years among groups independent of the kind of treatment; however, there was a higher mortality rate in 3VD (p < 0.001). When we stratified our analysis for each treatment option, bypass surgery was associated with a tower number of composite end-point in all groups (SVD p < 0.001, 2VD p = 0.002, 3VD p < 0.001). In multivariate analysis, we found higher mortality risk in 3VD comparing to SVD (p = 0.005, HR 3.14, 95%Cl 1.4-7.0). Conclusion: Three-vessel disease was associated with worse prognosis compared to single-or two-vessel disease in patients with stable coronary disease and preserved ventricular function at 5-year follow-up. In addition, event-free survival rates were higher after bypass surgery, independent of the number of vessels diseased in these subsets of patients. (c) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Acute and Chronic Effects of Epicardial Radiofrequency Applications Delivered on Epicardial Coronary Arteries

Background-Epicardial coronary injury is by far the most feared complication of epicardial ablation. Little information is available regarding the chronic effects of delivering radiofrequency in the vicinity of large coronary vessels, and the long-term impact of this approach for mapping and ablation on epicardial vessel integrity is poorly understood. Therefore, the aim of this study was to characterize the acute and chronic histopathologic changes produced by in vivo epicardial pulses of radiofrequency ablation on coronary artery of porcine hearts. Methods and Results-Seven pigs underwent a left thoracotomy. The catheter was sutured adjacent to the left anterior descending artery and left circumflex artery, and 20 pulses of radiofrequency energy were applied. Radiofrequency lesions located no more than 1 mm of the vessel were used for this analysis. Three animals were euthanized 20 days (acute phase) after the procedure and 4 animals after 70 days (chronic phase). The following parameters were obtained in each vessel analyzed: (1) internal and external perimeter; (2) vessel wall thickness; (3) tunica media thickness, and (4) tunica intima thickness. The presence of adipose tissue around the coronary arteries, the distance between the artery and the epicardium, and the anatomic relationship of the artery with the coronary vein was also documented for each section. Sixteen of 20 (80%) sections analyzed, showed intimal thickening with a mean of 0.18 +/- 0.14 mm compared with 0.13 +/- 0.16 mm in the acute phase (P=0.331). The mean tunica media thickness was 0.25 +/- 0.10 mm in the chronic phase animals compared with 0.18 +/- 0.03 mm in the acute phase animals (P=0.021). A clear protective effect of pericardial fat and coronary veins was also present. A positive correlation between depth of radiofrequency lesion and the degree of vessel injury expressed as intimal and media thickening (P=0.001) was present. A negative correlation was identified (r = -0.83; P=0.002) between intimal thickening and distance between epicardium and coronary artery. Conclusions-In this porcine model of in vivo epicardial radiofrequency ablation in proximity to coronary arteries leads to acute and chronic histopathologic changes characterized by tunica intima and media thickening, with replacement of smooth muscle cells with extracellular matrix, but no significant stenosis was observed up to 70 days after the ablation. The absence of acute coronary occlusion or injury does not preclude subsequent significant arterial damage, which frequently occurs when epicardial radiofrequency applications are delivered in close vicinity to the vessels. (Circ Arrhythm Electrophysiol. 2011;4:526-531.)

Glycemia and prognosis of patients with chronic heart failure-Subanalysis of the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial

Background Heart failure and diabetes often occur simultaneously in patients, but the prognostic value of glycemia in chronic heart failure is debatable. We evaluated the role of glycemia on prognosis of heart failure. Methods Outpatients with chronic heart failure from the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial were grouped according to the presence of diabetes and level of glycemia. All-cause mortality/heart transplantation and unplanned hospital admission were evaluated. Results Four hundred fifty-six patients were included (135 [29.5%] female, 124 [27.2%] with diabetes mellitus, age of w50.2 +/- 11.4 years, and left-ventricle ejection fraction of 34.7% +/- 10.5%). During follow-up (3.6 +/- 2.2 years), 27 (5.9%) patients were submitted to heart transplantation and 202 (44.2%) died; survival was similar in patients with and without diabetes mellitus. When patients with and without diabetes were categorized according to glucose range (glycemia <= 100 mg/dL [5.5 mmol/L]), as well as when distributed in quintiles of glucose, the survival was significantly worse among patients with lower levels of glycemia. This finding persisted in Cox proportional hazards regression model that included gender, etiology, left ventricle ejection fraction, left ventricle diastolic diameter, creatinine level and beta-blocker therapy, and functional status (hazard ratio 1.45, 95% CI 1.09-1.69, P = .039). No difference regarding unplanned hospital admission was found. Conclusion We report on an inverse association between glycemia and mortality in outpatients with chronic heart failure. These results point to a new pathophysiologic understanding of the interactions between diabetes mellitus, hyperglycemia, and heart disease. (Am Heart J 2010; 159: 90-7.)

Association between ADAMTS13 polymorphisms and risk of cardiovascular events in chronic coronary disease

Introduction: Association between ADAMTS13 levels and cardiovascular events has been described recently. However, no genetic study of ADAMTS13 in coronary patients has been described. Materials and Methods: Based on related populations frequencies and functional studies, we tested three ADAMTS13 polymorphisms: C1342G (Q448E), C1852G (P618A) and C2699T (A900V) in a group of 560 patients enrolled in the Medical, Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. The incidence of the 5-year end-points of death and death from cardiac causes, myocardial infarction, refractory angina requiring revascularization and cerebrovascular accident was determined for each polymorphim`s allele, genotype and haplotype. Risk was assessed with the use of logistic regression and Cox proportional-hazards model and multivariable adjustment was employed for possible confounders. Results: Clinical characteristics and received treatment of each genotype group were similar at baseline. In an adjusted model for cardiovascular risk variables, we were able to observe a significant association between ADAMTS13 900V variant and an increased risk of death (OR: 1,92 CI: 1,14-3,23, p = 0,015) or death from cardiac cause (OR: 2,67, CI: 1,59-4,49, p = 0,0009). No association between events and ADAMTS13 Q448E or P618A was observed. Conclusions: This first report studying the association between ADAMTS13 genotypes and cardiovascular events provides evidence for the association between ADAMTS13 900V variant and an increased risk of death in a population with multi-vessel CAD. (C) 2009 Elsevier Ltd. All rights reserved.

Effects of Exercise Training in Patients with Chronic Heart Failure and Sleep Apnea

Study Objectives: To test the effects of exercise training on sleep and neurovascular control in patients with systolic heart failure with and without sleep disordered breathing. Design: Prospective interventional study. Setting: Cardiac rehabilitation and exercise physiology unit and sleep laboratory. Patients: Twenty-five patients with heart failure, aged 42 to 70 years, and New York Heart Association Functional Class I-III were divided into 1 of 3 groups: obstructive sleep apnea (n = 8), central sleep apnea (n 9) and no sleep apnea (n = 7). Interventions: Four months of no-training (control) followed by 4 months of an exercise training program (three 60-minute, supervised, exercise sessions per week). Measures and Results: Sleep (polysomnography), microneurography, forearm blood flow (plethysmography), peak VO(2). and quality of life were evaluated at baseline and at the end of the control and trained periods. No significant changes occurred in the control period. Exercise training reduced muscle sympathetic nerve activity (P < 0.001) and increased forearm blood flow (P < 0.01), peak VO(2) (P < 0.01), and quality of life (P < 0.01) in all groups, independent of the presence of sleep apnea. Exercise training improved the apnea-hypopnea index, minimum O(2) saturation, and amount stage 3-4 sleep (P < 0.05) in patients with obstructive sleep apnea but had no significant effects in patients with central sleep apnea. Conclusions. The beneficial effects of exercise training on neurovascular function, functional capacity, and quality of life in patients with systolic dysfunction and heart failure occurs independently of sleep disordered breathing. Exercise training lessens the severity of obstructive sleep apnea but does not affect central sleep apnea in patients with heart failure and sleep disordered breathing.

Risk factors for Chagas` disease reactivation after heart transplantation

Background: Chagas` disease is the illness caused by the protozoan Trypanosoma cruzi and it is still endemic in Latin America. Heart transplantation is a therapeutic option for patients with end-stage Chagas` cardiomyopathy. Nevertheless, reactivation may occur after transplantation, leading to higher morbidity and graft dysfunction. This study aimed to identify risk factors for Chagas` disease reactivation episodes. Methods: This investigation is a retrospective cohort study of all Chagas` disease heart transplant recipients from September 1985 through September 2004. Clinical, microbiologic and histopathologic data were reviewed. Statistical analysis was performed with SPSS (version 13) software. Results: Sixty-four (21.9%) patients with chronic Chagas` disease underwent heart transplantation during the study period. Seventeen patients (26.5%) had at least one episode of Chagas` disease reactivation, and univariate analysis identified number of rejection episodes (p = 0.013) and development of neoplasms (p = 0.040) as factors associated with Chagas` disease reactivation episodes. Multivariate analysis showed that number of rejection episodes (hazard ratio = 1.31; 95% confidence interval [CI]: 1.06 to 1.62; p = 0.011), neoplasms (hazard ratio = 5.07; 95% CI: 1.49 to 17.20; p = 0.009) and use of mycophenolate mofetil (hazard ratio = 3.14; 95% CI: 1.00 to 9.84; p = 0.049) are independent determinants for reactivation after transplantation. Age (p = 0.88), male gender (p = 0.15), presence of rejection (p = 0.17), cytomegalovirus infection (p = 0.79) and mortality after hospital discharge (p = 0.15) showed no statistically significant difference. Conclusions: Our data suggest that events resulting in greater immunosuppression status contribute to Chagas` disease reactivation episodes after heart transplantation and should alert physicians to make an early diagnosis and perform pre-emptive therapy. Although reactivation led to a high rate of morbidity, a low mortality risk was observed.

Continuous positive airway pressure increases inspiratory capacity of COPD patients

Background and objective: Hyperinflation with a decrease in inspiratory capacity (IC) is a common presentation for both unstable and stable COPD patients. As CPAP can reduce inspiratory load, possibly secondary to a reduction in hyperinflation, this study examined whether CPAP would increase IC in stable COPD patients. Methods: Twenty-one stable COPD patients (nine emphysema, 12 chronic bronchitis) received a trial of CPAP for 5 min at 4, 7 and 11 cmH(2)O. Fast and slow VC (SVC) were measured before and after each CPAP trial. In patients in whom all three CPAP levels resulted in a decreased IC, an additional trial of CPAP at 2 cmH(2)O was conducted. For each patient, a `best CPAP` level was defined as the one associated with the greatest IC. This pressure was then applied for an additional 10 min followed by spirometry. Results: Following application of the `best CPAP`, the IC and SVC increased in 15 patients (nine emphysema, six chronic bronchitis). The mean change in IC was 159 mL (95% CI: 80-237 mL) and the mean change in SVC was 240 mL (95% CI: 97-386 mL). Among these patients, those with emphysema demonstrated a mean increase in IC of 216 mL (95% CI: 94-337 mL). Six patients (all with chronic bronchitis) did not demonstrate any improvement in IC. Conclusions: The best individualized CPAP can increase inspiratory capacity in patients with stable COPD, especially in those with emphysema.

Low-Level Laser Therapy in Chronic Autoimmune Thyroiditis: A Pilot Study

Background and Objectives: Chronic autoimmune thyroiditis (CAT) remains the most common cause of acquired hypothyroidism There is currently no therapy that is capable of regenerating CAT-damaged thyroid tissue The objective of this study was to gauge the value of applying low-level laser therapy (LLLT) in CAT patients based on both ultrasound studies (USs) and evaluations of thyroid function and thyroid autoantibodies. Study Design/Materials and Methods: Fifteen patients who had hypothyroidism caused by CAT and were undergoing levothyroxine (LT4) treatment were selected to participate in the study Patients received 10 applications of LLLT (830 nm, output power 50 mW) in continuous mode, twice a week, using either the punctual technique (8 patients) or the sweep technique (7 patients), with fluence in the range of 38-108 J/cm(2) USs were performed prior to and 30 days after LLLT USs included a quantitative analysis of echogenicity through a gray-scale computerized histogram index (El). Following the second ultrasound (30 days after LLLT), LT4 was discontinued in all patients and, if required, reintroduced Truodothyronine, thyroxine (T4), free T4, thyrotropin, thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies levels were assessed before LLLT and then 1, 2, 3, 6, and 9 months after LT4 withdrawal. Results: We noted all patients` reduced LT4 dosage needs, including 7 (47%) who did not require any LT4 through the 9-month follow-up The LT4 dosage used pre-LLLT (96 +/- 22 mu g/day) decreased in the 9th month of follow-up (38 23 mu g/day; P<0.0001) TPOAb levels also decreased (pre-LLLT = 982 +/- 530 U/ml, post-LLLT = 579 454 U/ml, P = 0 016) TgAb levels were not reduced, though we did observe a post-LLLT increase in the EI (pre-LLLT = 0 99 +/- 0.09, post-LLLT= 1.21 +/- 0.19, P=0.001) Conclusion: The preliminary results indicate that LLLT promotes the improvement of thyroid function, as patients experienced a decreased need for LT4, a reduction in TPOAb levels, and an increase in parenchymal echogenicity Lasers Surg. Med. 42:589-596, 2010. (C) 2010 Wiley-Liss, Inc

Prevalence of fibromyalgia and chronic widespread pain in community-dwelling elderly subjects living in Sao Paulo, Brazil

Objectives: To estimate the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in community-dwelling elderly individuals living in Sao Paulo, to assess the spectrum of problems related to these diseases using the Fibromyalgia Impact Questionnaire (FIQ) and to correlate the FIQ with the number of tender points and with pain threshold. Methods: Our sample consisted of 361 individuals (64% women, 36% men, mean age of 73.3 +/- 5.7 years). Individuals were classified into four groups: FM (according to American College of Rheumatology criteria), CWP, regional pain (RP) and no pain (NP). Pain characteristics and dolorimetry for 18 tender points and the FIQ were assessed. Results: The prevalence of FM was 5.5% [95% confidence interval (CI) = 5.4-5.7], and the prevalence of CWP was 14.1% (95% Cl: 10.5-17.7%). The frequency of RP was 52.6% and the prevalence of NP was 27.7%. FIQ scores were higher in people with FM (44.5), followed by CWP (31.4), RP (18.1) and NP (5.5) (p < 0.001). There was a positive correlation between the domains of the FIQ and the number of tender Points (p < 0.05), and a negative correlation between FIQ score and pain threshold (p < 0.05). Conclusion: In our elderly subjects, the prevalence of FM was slightly higher compared to previously reported studies, and CWP was around 14%. The spectrum of problems related to chronic pain was more severe in FM followed by CWP, strongly suggesting that these conditions should be diagnosed and adequately treated in older individuals. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Aerobic training reverses airway inflammation and remodelling in an asthma murine model

Aerobic training (AT) decreases dyspnoea and exercise-induced bronchospasm, and improves aerobic capacity and quality of life; however, the mechanisms for such benefits remain poorly understood. The aim of the present study was to evaluate the AT effects in a chronic model of allergic lung inflammation in mice after the establishment of airway inflammation and remodelling. Mice were divided into the control group, AT group, ovalbumin (OVA) group or OVA+AT group and exposed to saline or OVA. AT was started on day 28 for 60 min five times per week for 4 weeks. Respiratory mechanics, specific immunoglobulin (Ig)E and IgG(1), collagen and elastic fibres deposition, smooth muscle thickness, epithelial mucus, and peribronchial density of eosinophils, CD3+ and CD4+, IL-4, IL-5, IL-13, interferon-gamma, IL-2, IL-1ra, IL-10, nuclear factor (NF)-kappa B and Foxp3 were evaluated. The OVA group showed an increase in IgE and IgG1, eosinophils, CD3+, CD4+, IL-4, IL-5, IL-13, NF-kappa B, collagen and elastic, mucus synthesis, smooth muscle thickness and lung tissue resistance and elastance. The OVA+AT group demonstrated an increase of IgE and IgG(1), and reduction of eosinophils, CD3+, CD4+, IL-4, IL-5, IL-13, NF-kappa B, airway remodelling, mucus synthesis, smooth muscle thickness and tissue resistance and elastance compared with the OVA roup (p < 0.05). The OVA+AT group also showed an increase in IL-10 and IL-1ra (p < 0.05), independently of Foxp3. AT reversed airway inflammation and remodelling and T-helper cell 2 response, and improved respiratory mechanics. These results seem to occur due to an increase in the expression of IL-10 and IL-1ra and a decrease of NF-kappa B.

Furosemide impairs nasal mucociliary clearance in humans

Furosemide, a potent diuretic, affects ion and water movement across the respiratory epithelium. However, the effects of furosemide, as clinically used, on mucociliary clearance, a critical respiratory defense mechanism, are still lacking in humans. Fourteen young healthy subjects were assigned to three random interventions, spaced one-week apart: no intervention (control), oral furosemide (40 mg), and furosemide + oral volume replacement (F + R). Nasal mucociliary clearance was assessed by saccharine test (STT), and mucus properties were in vitro evaluated by means of contact angle and transportability by sneeze. Urine output and osmolality were also evaluated. Urine output increased and reduced urine osmolality in furosemide and F + R compared to the control condition. STT remained stable in the control group. In contrast, STT increased significantly (40%) after furosemide and F + R. There were no changes in vitro mucus properties in all groups. In conclusion, furosemide prolongs STT in healthy young subjects. This effect is not prevented by fluid replacement, suggesting a direct effect of furosemide on the respiratory epithelium. (C) 2010 Elsevier B.V. All rights reserved.