Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease of unknown etiology with only two federally approved drug options. Given the complex molecular pathogenesis of IPF involving multiple cell types and multiple pathways, we explore the effects of a potential antifibrotic and antioxidant drug combination. Curcumin is a polyphenolic compound derived from turmeric with significant biological activity including a potential antifibrotic capacity. N-acetylcysteine (NAC) is a precursor to the antioxidant glutathione. To advance our understanding of these molecules, and to identify a clinical application, we present a small number of focused experiments that interrogates the effect of curcumin and NAC on pathways relevant to IPF in both fibroblasts and epithelial cells. METHODS: Primary epithelial cell and fibroblasts isolated from patients with IPF were challenged with a combination treatment of NAC and curcumin. Evaluation of the antifibrotic potential and effect on oxidative stress was performed through QPCR gene expression analysis and functional assays including scratch tests, viability assays, and measurement of induced reactive oxygen species. RESULTS: We demonstrate that curcumin alone does have antifibrotic potential, but that effect is accompanied by proapoptotic increases in oxidative stress. Coupled with this, we find that NAC alone can reduce oxidative stress, but that epithelial cell viability is decreased through this treatment. However, co-administration of these two molecules decreases oxidative stress and maintains high cell viability in both cell types. In addition, this co-treatment maintains an antifibrotic potential. CONCLUSIONS: These findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.

Lung cancer risk test trial: study design, participant baseline characteristics, bronchoscopy safety, and establishment of a biospecimen repository.

BACKGROUND: The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository. METHODS/DESIGN: Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, peripheral blood samples, baseline CT, and medical and demographic data were collected from each subject. DISCUSSION: Over a two-year span (2010-2012), 403 subjects were enrolled at 12 sites. At baseline 384 subjects remained in study and mean age and smoking history were 62.9 years and 50.4 pack-years respectively, with 34% current smokers. Obstructive lung disease (FEV1/FVC <0.7) was present in 157 (54%). No severe adverse events were associated with bronchoscopic brushing. An NBEC and matched peripheral blood bio-specimen repository was established. The demographic composition of the enrolled group is representative of the population for which the LCRT is intended. Specifically, based on baseline population characteristics we expect lung cancer incidence in this cohort to be representative of the population eligible for low-dose Computed Tomography (LDCT) lung cancer screening. Collection of NBEC by bronchial brush biopsy/bronchoscopy was safe and well-tolerated in this population. These findings support the feasibility of testing LCRT clinical utility in this prospective study. If validated, the LCRT has the potential to significantly narrow the population of individuals requiring annual low-dose helical CT screening for early detection of lung cancer and delay the onset of screening for individuals with results indicating low lung cancer risk. For these individuals, the small risk incurred by undergoing once in a lifetime bronchoscopic sample collection for LCRT may be offset by a reduction in their CT-related risks. The LCRT biospecimen repository will enable additional studies of genetic basis for COPD and/or lung cancer risk. TRIAL REGISTRATION: The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010.

Artificial Intelligence in Surgical Evaluation: A Study of Facial Rejuvenation Techniques.

Background: Aesthetic facial surgeries historically rely on subjective analysis in determining success; this limits objective comparison of surgical outcomes. Objectives: This case study exemplifies the use of an artificial intelligence software on objectively analyzing facial rejuvenation techniques with the aim of reducing subjective bias. Methods: Retrospectively, all patients who underwent facial rejuvenation surgery with concomitant procedures from 2015 to 2017 were included (n = 32). Patients were categorized into Groups A to C: Group A-10 superficial musculoaponeurotic system (SMAS) plication facelift (n = 10), Group B-SMASectomy facelift (n = 7), and Group C-high SMAS facelift (n = 15). Neutral repose images preoperatively and postoperatively (average >3 months) were analyzed using artificial intelligence for emotion and action unit alterations. Results: Postoperatively, Group A experienced a decrease in happiness by 0.84% and a decrease in anger by 6.87% (P >> .1). Group B had an increase in happiness by 0.77% and an increase in anger by 1.91% (P >> .1). Both Group A and Group B did not show any discernable action unit patterns. In Group C, the lip corner puller AU increased in average intensity from 0% to 18.7%. This correlated with an average increase in detected happiness from 1.03% to 13.17% (P = .008). Conversely, the average detected anger decreased from 14.66% to 0.63% (P = .032). Conclusions: This study provides the first proof of concept for the use of a machine learning software application to objectively assess various aesthetic surgical outcomes in facial rejuvenation. Due to limitations in patient heterogeneity, this study does not claim one technique's superiority but serves as a conceptual foundation for future investigation.

Impact of Surgical Rejuvenation on Visual Processing and Character Attribution of Faces.

Background: This study considers observers' reflexive responses to the rejuvenated face, and how instinctive responses relate to subjective judgment. We investigated observers' reflexive perception of faces both pre and post surgical intervention during the early stages of visual processing. Subjective character attribution for all test images was also assessed by the same observers. Method: Forty frontal facial images of 20 patients portraying the pre- and postoperative high superficial musculoaponeurotic system facelift along with variable concomitant procedures were studied. Nineteen lookzone regions were mapped post hoc onto each image. Forty observers examined the images, whereas an eye-tracking camera recorded their eye movements. Visual fixation data were recorded and analyzed. Observers also rated each image on the basis of five elemental positive character attributes. Results: A statistically coherent but nonsignificant (P > 0.05) trend was identified with the surgical intervention resulting in greater attention being paid to the central triangle region of the face with reduction in attention to the facial periphery. Facial rejuvenation significantly increased the subjective character ratings of all five positively valenced attributes tested. Average age estimate of the photos decreased significantly from 54 to 48.6 years (true average age of 57.4 years). Conclusions: We provide data illustrating both reflexive and subjective responses to facial rejuvenation. Observers reported a more favorable impression of the treated faces and evaluated them as being younger than their true age. A trend was detected for increased visual fixation of the central facial region following rejuvenation. Interpretation of these findings and indication for further research is provided.

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterised by myofibroblast proliferation leading to architectural destruction. Neither the origin nor the continued proliferation of myofibroblasts is well understood. Explanted human IPF lungs were stained by immunohistochemistry for calretinin, a marker of pleural mesothelial cells (PMCs). Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) lungs acted as controls. The number of PMCs per 100 nucleated cells and per photomicrograph was estimated along with the Ashcroft score of fibrosis. Mouse PMCs expressing green fluorescent protein (GFP) or labelled with nanoparticles were injected into the pleural space of mice given intranasal transforming growth factor (TGF)-ß1. Mouse lungs were lavaged and examined for the presence of GFP, smooth muscle α-actin (α-SMA) and calretinin. Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF lungs. The number of PMCs correlated with the Ashcroft score. In mice, nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on the TGF-ß1 dose. Fluorescent staining showed α-SMA expression in GFP-expressing PMCs, with co-localisation of GFP and α-SMA. PMCs can traffic through the lung and show myofibroblast phenotypic markers. PMCs are present in IPF lungs, and their number correlates with IPF severity. Since IPF presumably begins subpleurally, PMCs could play a pathogenetic role via mesothelial-mesenchymal transition.

Pulmonary hypertension in patients with bronchiolitis obliterans syndrome listed for retransplantation.

Bronchiolitis Obliterans Syndrome (BOS) is a major cause of morbidity and mortality post-lung transplantation. Pulmonary hypertension (PH) may complicate the course of patients with advanced lung disease. We sought to characterize the prevalence of PH in patients with BOS. We performed a retrospective analysis of lung transplant recipients with BOS relisted for transplantation with the United Network for Organ Sharing (UNOS). Right heart catheterization (RHC) data were required for analysis. Eighty patients with BOS qualified for the analysis. PH was present in 32.5% of patients with an average mean pulmonary artery pressure (mPAP) of 32.3 mmHg (range: 26-63 mmHg). Of these, 42.3% had an elevated pulmonary capillary wedge pressure. There was no difference in PH prevalence between bilateral (26.5%) and single lung recipients (41.9%), nor did it differ by primary disease. There was no correlation between pulmonary function data and the presence or severity of PH. There was no difference in oxygen requirements or 6-min walk distance between patients with and without PH. This is the first report of PH in patients with BOS. Many of these cases occur in association with diastolic dysfunction. Although no impact on functional status or outcomes was discerned, further studies appear warranted.

Pulmonary hypertension in interstitial lung disease.

Pulmonary hypertension (PH) may complicate the course of many forms of advanced interstitial lung disease (ILD) and has been shown to portend a worse outcome. The aetiology of PH is likely multifactorial with variable contribution of factors amongst the different diseases. The most common such conditions include idiopathic pulmonary fibrosis, sarcoidosis, connective tissue disease-related ILD and pulmonary langerhans cell histiocytosis. Whether the course and impact of PH in these conditions can be modified by therapy requires further study.

Work of breathing after extubation.

Recently we showed that work of breathing was higher in the immediate period after extubation as compared with spontaneous breathing through an endotracheal tube. In this study, we evaluated the glottis and trachea as potential sites of increased airway resistance after extubation. We measured breathing pattern, work of breathing, and pressure time product in eight patients during weaning from mechanical ventilation. We acquired data during pressure support ventilation and spontaneous breathing via the ventilator, with the endotracheal tube in place, and after extubation. During bronchoscopy at the time of extubation, we examined the trachea and measured the cross-sectional area of the glottis. Work of breathing and pressure time product were significantly lower during pressure support ventilation as compared with spontaneous breathing after extubation (0.43 +/- 0.10 vs 1.49 +/- 0.10 J/L and 101 +/- 22 vs 299 +/- 30 cm H2O.s/min, respectively; p < 0.05). However, both indexes were significantly higher after extubation as compared with breathing through the endotracheal tube (1.49 +/- 0.10 vs 0.95 +/- 0.12 J/L, 299 +/- 31 vs 196 +/- 26 cm H2O.s/min respectively; p < 0.05). During bronchoscopy, no tracheal or glottic narrowing was detected. The glottic cross-sectional area was successfully measured in four patients at the onset of inspiration and found to be 140 +/- 15 mm2. This value was larger than the mean cross-sectional area of the endotracheal tubes used in these patients (50 mm2). We conclude that neither tracheal nor laryngeal disease caused the increase in work of breathing after extubation. Our data suggest that upper airway narrowing at a more proximal site, such as the oropharynx or velopharynx may be the cause of the increase in respiratory work.

Aspergillus and endobronchial abnormalities in lung transplant recipients.

STUDY OBJECTIVE: To determine the relationship between aspergillus recovery from the airways of lung transplant recipients and the development of endobronchial abnormalities. DESIGN: Retrospective case series. SETTING: Tertiary-care hospital. PATIENTS: All patients who underwent lung transplantation between December 1991 and June 1999. MEASUREMENTS AND RESULTS: The study cohort included 38 patients. The primary end point was the bronchoscopic identification of an endobronchial abnormality. Aspergillus was isolated from the lungs of nine patients (23.7%). Most of these isolates occurred early after transplantation (mean, 8 weeks). Endobronchial abnormalities arose in seven of the patients (18.4%) and manifested as either exuberant granulation tissue or stricture formation. Six of the 9 (66.6%) patients with aspergillus developed airway lesions, compared to 1 of the 29 patients (3.4%) without aspergillus (p = 0.0002). Endobronchial abnormalities were 19.3 times more likely to occur in patients in whom aspergillus had previously been isolated. As a screening test for the subsequent diagnosis of an airway complication, the recovery of aspergillus had a sensitivity and specificity of 85.7% and 90.3%, respectively. These aspergillus-related endobronchial abnormalities were clinically relevant as evidenced by a mean increase of 25.9% in the FEV(1) after bronchoscopic intervention. CONCLUSION: The early isolation of aspergillus from the airways of lung transplant recipients identifies patients at increased risk for the development of clinically significant endobronchial abnormalities.

Prediction of minimal pressure support during weaning from mechanical ventilation.

Our goal was to evaluate the accuracy of a prediction equation that estimates the minimal level of pressure support (PS) required to overcome the resistance of the ventilator circuit and the endotracheal tube during mechanical ventilation. We calculated the minimal PS (PSmin) by means of the relationship between airway resistance and peak inspiratory flow rate during mechanical ventilation. Measurements of breathing pattern, flow rates, work of breathing (WOB), pressure time product (PTP), and PEEPi were made during several modes of ventilation (PSmin, PSmin + 25 percent, PSmin-25 percent, flow by, CPAP 0 cm H2O) and while breathing through an endotracheal tube (ETT) and spontaneous breathing (EXT). The WOB was significantly higher during EXT than PSmin, PSmin-25 percent, and ETT (1.04 vs 0.45, 0.54, and 0.74 J/L, respectively, p < 0.05). An unexpected finding was a higher WOB and PTP during EXT as compared with ETT in six of seven of our patients (1.04 vs 0.74 J/L). Examination of breathing pattern and flow volume loops in these two breathing modes raises the possibility that the post-EXT pathology increases in WOB is related to upper airway abnormality. Because of this, our predicted PSmin underestimated the WOB required for spontaneous breathing immediately post EXT.

Delayed development of obliterative bronchiolitis syndrome with OKT3 after unilateral lung transplantation. A plea for multicenter immunosuppressive trials.

There is no consensus regarding the optimal induction immunosuppression regimen after lung transplantation (LT). In addition to the potential benefit of a reduced incidence of early acute allograft rejection, cytolytic induction immunosuppression may impact on long-term allograft function. We retrospectively assessed our incidence of obliterative bronchiolitis syndrome (OBS) stages Ia and IIa in LT survivors given two different cytolytic induction immunosuppression regimens: (between March 1989 and October 1990) OKT3 (5 mg/d)x10 to 14 days (n=11) vs (between November 1990 and April 1993) Minnesota antilymphocyte globulin (MALG) (10 to 15 mg/kgdx5 to 7 days. Cyclosporine (CSA) (whole blood polyclonal assay=600 to 800 ng/mL), azathioprine (1 to 2 mg/kg/d), and maintenance prednisone (0.2 mg/kg/d) were similar. Surveillance spirometry was performed monthly, in accordance with accepted American Thoracic Society criteria. Fiberoptic bronchoscopy with transbronchial biopsies (TBBs) were performed for clinical indications. Surveillance TBBs were not performed during the era of this study. As defined by the ISHLT "Working Formulation for the Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts," latencies to development of OBS stages Ia and IIa were determined by Kaplan-Meir analysis. Stepwise regression (Cox proportional hazards model) was performed for the variables: cytolytic induction regimen, episodes cytomegalovirus (CMV) pneumonitis, episodes CMV infection, serologic CMV donor (+): recipient (-) mismatch, prior pregnancy, HLA (A,B,DR +/- DQ) mismatches, episodes greater than grade A1 acute cellular rejection (ACR). We found that the OKT3 cohort experienced longer latencies for OBS stages Ia and IIa. Latencies to OBS stages Ia for OKT3 ve MALG were 962 +/- 65 vs 354 +/- 85 days (X +/- SEM) respectively. Brookmeyer-Crowley 95% confidence intervals for median latencies were 744 to 1,180 vs 266 to 510 days for OKT3 vs MALG, respectively. The Cox model was significant only for the variable of the induction cytolytic immunosuppression regimen (p=0.0015). By physiologic criteria, a longer course of OKT3 appeared superior to the short-course MALG protocol in delaying chronic lung allograft dysfunction. These effects may be related either to inherent differences in the antilymphocyte preparations or, alternatively, the difference in duration of treatment between groups. Surveillance TBB and treatment of detected occult ACR may serve to negate the observed differences in latencies for OBS.

Utility of inhaled pentamidine prophylaxis in lung transplant recipients.

The incidence of Pneumocystis carinii pneumonia (PCP) has been shown to be high posttransplantation in the absence of prophylaxis. For this reason, lung transplant recipients routinely receive prophylaxis. We report on our results using aerosolized pentamidine prophylaxis in nine patients post-lung transplantation (eight single lung transplants, one double). The patients received monthly treatments of 300 mg of aerosolized pentamidine for a mean of 10.6 months (range, 4 to 21 months). Patients were routinely monitored with serial pulmonary function studies and bronchoscopy as clinically indicated. Two of the patients experienced bronchospasm in response to the therapy. None of the patients experienced any episodes of PCP during the period of inhaled pentamidine prophylaxis. Inhaled pentamidine is a safe and effective form of PCP prophylaxis and may be used instead of sulfamethoxazole-trimethoprim in patients who have a sulfa allergy or other untoward sulfa side effects.

Bronchiolitis obliterans in single-lung transplant recipients.

The presentation and clinical course of bronchiolitis obliterans (BO) in single-lung transplant (SLT) recipients has thus far not been well described. We retrospectively analyzed the serial spirometry of 15 SLT patients with BO. All the patients fulfilled the criteria for BO syndrome, and 11 of the 15 had histologically documented BO. Based on serial FEV1 analysis, we identified three patterns of presentation and progression of BO. The first pattern (n = 6) was characterized by a rapid onset and a relentless progressive course; the second pattern (n = 5) was characterized by a similar rapid onset and initial rapid decline, but was followed by stabilization in lung function; the third pattern (n = 4) was characterized by an insidious onset and course. In all patients, a permanent reduction in the mean forced expiratory flow during the middle half of the forced vital capacity appeared to be an early sensitive index for the development of BO. An appreciation of these different modes of presentation and progression of BO is potentially important in the assessment of prognosis and management of the SLT recipient.

Successful use of cyclosporine in a lung transplant recipient with tacrolimus-associated hemolytic uremic syndrome.

Hemolytic-uremic syndrome (HUS) is a rare, but well-described complication in organ transplant recipients maintained on cyclosporine immunosuppression. Tacrolimus is a newer agent with similar immunosuppressant efficacy. In cases of cyclosporine-related HUS in renal transplant recipients, tacrolimus has been used successfully without recurrence of HUS. Tacrolimus has been reported to cause HUS in renal and more recently in cardiac transplant patients. We report a case of HUS in a lung transplant recipient receiving tacrolimus who was subsequently converted to cyclosporine without recurrence of HUS.

Obstructive flow-volume loop contours after single lung transplantation.

The development of spirometric airflow obstruction may be a diagnostic dilemma in recipients of single lung allografts. The contribution of bronchial anastomotic stenosis to the observed spirometric obstruction may be clinically difficult to distinguish from that of obliterative bronchiolitis. Similarly, differentiating the "normal" obstructive defect after single lung transplantation for emphysema from obliterative bronchiolitis may be clinically challenging. We retrospectively reviewed the maximum inspiratory and expiratory flow-volume loop contours of lung transplant recipients with either obliterative bronchiolitis (n = 7) or bronchoscopically diagnosed severe bronchial anastomotic stenosis (n = 3). Five patients underwent single lung transplantation for obstructive native lung diseases and underwent observation before and after development of obliterative bronchiolitis. Bronchial anastomotic stenosis-maximum inspiratory and expiratory flow-volume loops were analyzed both before and after correction of stenosis by niobium: yttrium-aluminum-garnet laser photoresection or endobronchial silicone stent placement. Measures of airflow derived from maximum inspiratory and expiratory flow-volume loops, such as peak expiratory flow, peak inspiratory flow, forced expiratory flow at 50% vital capacity, forced inspiratory flow at 50% vital capacity, and forced expiratory volume in 1 second/peak expiratory flow ratio could not differentiate patients with bronchial anastomotic stenosis versus obliterative bronchiolitis. The most clinically useful index was the maximum inspiratory and expiratory flow-volume contour, which was characterized by terminal plateaus during exhalation and inhalation in patients with bronchial anastomotic stenosis. This index was reflected in a lower forced inspiratory flow at 75% vital capacity and forced inspiratory flow at 75% vital capacity/peak inspiratory flow ratio in bronchial anastomotic stenosis that increased after elimination of the anastomotic obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential soluble interleukin-2R levels in bilateral bronchoalveolar lavage after single lung transplantation.

Preliminary reports suggest that measurement of the soluble 55 kd subunit of the interleukin-2 receptor may facilitate the diagnosis of allograft rejection in solid organ transplants. Levels of soluble interleukin-2 receptor in serum or plasma have previously lacked sufficient sensitivity and specificity for the diagnosis of acute allograft rejection. Because single lung transplantation is preferentially performed for nonseptic end-stage pulmonary and cardiopulmonary maladies, we questioned whether the pattern of soluble interleukin-2 receptor recovery in bronchoalveolar lavage fluid obtained from both the native and transplanted lungs may enhance correct diagnosis. Fifty-three consecutive fiberoptic bronchoscopic procedures were performed with bilateral bronchoalveolar lavage fluid. Transbronchoscopic biopsies were histologically classified by the International Society for Heart Transplantation Working Formulation for Standardized Nomenclature. "Soluble interleukin-2 receptor index" was calculated as the quotient of soluble interleukin-2 receptor (in units per milliliter) by enzyme-linked immunosorbent assay, divided by protein (in milligrams per milliliter) to correct for differences in bronchoalveolar lavage fluid techniques and cellularity. Soluble interleukin-2 receptor indexes were significantly increased in the allograft bronchoalveolar lavage fluid during histologic grade A (acute rejection) versus normal transbronchoscopic biopsy specimens (3395 +/- 1298 U/mg versus 76 +/- 21 U/mg) associated with an increased transplanted/native lung ratio (69.9 +/- 46 versus 2 +/- 1 [mean +/- standard error of the mean]) (one-way analysis of variance, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant.

Pulmonary hypertension (PH) may complicate idiopathic pulmonary fibrosis (IPF) but the prevalence of PH in IPF remains undefined. The present authors sought to describe the prevalence of PH in IPF. The lung transplant registry for the USA (January 1995 to June 2004) was analysed and IPF patients who had undergone right heart catheterisation (RHC) were identified. PH was defined as a mean pulmonary arterial pressure ((Ppa)) > or =25 mmHg and severe PH as a (Ppa) >40 mmHg. Independent factors associated with PH were determined. Of the 3,457 persons listed, 2,525 (73.0%) had undergone RHC. PH affected 46.1% of subjects; approximately 9% had severe PH. Variables independently associated with mild-to-moderate PH were as follows: need for oxygen, pulmonary capillary wedge pressure (P(pcw)) and forced expiratory volume in one second (FEV(1)). Independent factors related to severe PH included the following: carbon dioxide tension, age, FEV(1), P(pcw), need for oxygen and ethnicity. A sensitivity analysis in subjects with P(pcw) <15 mmHg did not appreciably alter the present findings. Pulmonary hypertension is common in idiopathic pulmonary fibrosis patients awaiting lung transplant, but the elevations in mean pulmonary arterial pressure are moderate. Lung volumes alone do not explain the pulmonary hypertension. Given the prevalence of pulmonary hypertension and its relationship with surrogate markers for quality of life (e.g. activities of daily living), future trials of therapies for this may be warranted.

Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics.

Pulmonary hypertension (PH) is a predictor of poor outcome in sarcoidosis. Little is known about the epidemiology of PH in sarcoidosis. The current authors reviewed the records of patients with sarcoidosis listed for lung transplantation in the USA between January 1995 and December 2002. PH was defined as a mean pulmonary artery pressure of >25 mmHg and severe PH as a mean pulmonary artery pressure of > or =40 mmHg. The cohort included 363 patients of whom 73.8% had PH. Neither spirometric testing nor the need for corticosteroids was associated with PH. Subjects with PH required more supplemental oxygen (2.7+/-1.8 L.min(-1) versus 1.6+/-1.4 L.min(-1)). The cardiac index was lower in individuals with PH, whereas the pulmonary capillary wedge pressure was higher. In multivariate analysis, supplemental oxygen remained an independent predictor of PH, whereas the relationship between cardiac index and PH was no longer significant. As a screening test, the need for oxygen had a sensitivity and specificity of 91.8% and 32.6%, respectively. Pulmonary hypertension is common in advanced sarcoidosis. The need for oxygen correlates with pulmonary hypertension. Since pulmonary hypertension is associated with poor outcomes and because simple clinical criteria fail to identify patients with sarcoidosis and pulmonary hypertension, more aggressive screening for this should be considered.

Ventilatory load characteristics during ventilatory muscle training.

The response of skeletal muscle to training is influenced by both the intensity and nature of the training stimulus. In this study we investigated the characteristics of the ventilatory load applied to the ventilatory muscles during several different modes of ventilatory muscle training. Patients with chronic obstructive pulmonary disease (COPD) performed the following breathing maneuvers: (1) Unloaded hyperpnea (UH), (2) resistive breathing through a fixed orifice (0.5 cm diameter) at frequencies of 15 and 30 breaths/min (RT15, RT30), (3) loaded breathing through a threshold valve set at 30% of the PImax at frequencies of 15 and 30 breaths/min (TT15, TT30), and (4) repetitive maximal inspiratory maneuvers against a closed shutter (PImax). During these maneuvers were recorded airflow and pressures at the month and esophagus, and from these measurements we derived VE and the work of breathing (WOB), tension time index (TTI), and pressure time product (PTP). The VE during UH was significantly higher than all other modes (p < 0.01), whereas the Pesmax was significantly lower during UH than during the resistive and loaded maneuvers (p < 0.01). The WOB did not differ during UH, TT30, and RT30, but was significantly higher in all three modes than at TT15 and RT15 (p < 0.05). During RT30 the TTI was higher than during TT30, TT15, and RT15 (p < 0.05), whereas the TTI during UH was significantly lower than during other maneuvers (p < 0.01). As expected, the highest Pesmax and PTP were found during the PImax maneuver. These data show that important qualitative differences in ventilatory muscle loading can be achieved by means of different devices and breathing strategies.(ABSTRACT TRUNCATED AT 250 WORDS)