Afroditi K. Boutou

Exercise capacity in idiopathic pulmonary fibrosis: the effect of pulmonary hypertension.

Background and objective:  Increased pulmonary arterial pressure (PAP) usually coexists with impaired lung function in IPF. Data on the effect of pulmonary hypertension (PH) on cardiopulmonary responses during exercise in IPF patients is very limited. We sought to investigate the impact of PH on exercise capacity and the correlation between systolic PAP (sPAP) and pulmonary function testing, as well as cardiopulmonary exercise parameters, in patients with IPF and PH.

Anemia of Chronic Disease in Chronic Obstructive Pulmonary Disease: A Case-Control Study of Cardiopulmonary Exercise Responses

Background: Anemia may be present in patients with chronic obstructive pulmonary disease (COPD) and further impair their functional capacity. Objectives: This study investigated the prevalence of anemia of chronic disease (ACD) in COPD patients and its impact on dyspnea and exercise capacity, utilizing cardiopulmonary exercise testing (CPET). Methods: ACD prevalence was assessed in 283 consecutive patients with stable COPD (263 males, 60 females; age 60.31 ± 5.34 years; percent forced expiratory volume in 1 s 46.94 ± 6.12). ACD diagnosis was based on a combination of clinical and laboratory parameters [hemoglobin (Hb) <13 g/dl for males, <12 g/dl for females; ferritin >30 ng/ml; total iron-binding capacity <250 µg/dl, and transferrin saturation rate between 15 and 50%]. Twenty-seven patients who were identified with ACD (cases) and 27 matched nonanemic patients (controls) completed maximal CPET, and data were compared between the groups. Results: ACD was diagnosed in 29 patients, which represents a prevalence of 10.24%; the severity of anemia was generally mild (mean Hb: 12.19 ± 0.66 g/dl). Patients with ACD had a higher Medical Research Council dyspnea score compared to controls (2.78 ± 0.44 vs. 2.07 ± 0.55; p <0.001) and lower peak O2 uptake (VO2) (59.54 ± 17.17 vs. 71.26 ± 11.85% predicted; p <0.05), peak work rate (54.94 ± 21.42 vs. 68.72 ± 20.81% predicted; p <0.05) and peak VO2/heart rate (69.07 ± 17.26 vs. 82.04 ± 18.22% predicted; p <0.05). There was also a trend for a lower anaerobic threshold (48.48 ± 15.16 vs. 55.42 ± 9.99% predicted; p = 0.062). No exercise parameter indicative of respiratory limitation differed between the groups. Conclusions: ACD occurs in approximately 10% of stable COPD patients and has a negative impact on dyspnea and circulatory efficiency during exercise.

Levels of inflammatory mediators in chronic obstructive pulmonary disease patients with anemia of chronic disease: a case–control study

BACKGROUND Although a subset of patients with chronic obstructive pulmonary disease (COPD) display anemia, the role of elevated pro-inflammatory cytokines in COPD-related anemia of chronic disease (ACD) has not been fully investigated. AIM To examine the levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), C-reactive protein (CRP) and erythropoietin in stable COPD outpatients with and without ACD. DESIGN A case-control design was followed. METHODS Fifty-four patients with stable COPD were studied. Among them, 27 had ACD according to strict clinical and laboratory criteria (group of cases), while another 27 nonanemic COPD patients, carefully matched to cases for age, gender, height, lung function and smoking status represented the controls. Serum levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, CRP and erythropoietin were measured in both groups. RESULTS Patients with ACD had significantly higher levels of IL-10 [25.6 (1.9-95.2) vs. 4.1 (1.9-31.9) pg/ml, P = 0.049] and IFNγ [15.2 (2.2-106.9) vs. 2 (1.2-18.3) pg/ml, P = 0.026] and had more frequently elevated CRP than controls. Levels of IL-1β [26.2 (9.8-96.4) vs. 7.9 (2.1-28.4) pg/ml, P = 0.073], IL-6 [20.3 (2.1-125.4) vs. 6.2 (1.2-33.8) pg/ml, P = 0.688] and TNFα [30.1 (3.2-107.5) vs. 10.1 (3.2-50.4) pg/ml, P = 0.131] were also higher in cases, but the differences did not reach statistical significance. Patients with ACD also displayed significantly higher erythropoietin levels than controls [(21.9 (8.4-101.7) vs. 9.7 (6.3-21.7) mIU/ml, P = 0.010], indicating erythropoietin resistance. CONCLUSION This study shows that in stable COPD outpatients with strictly defined ACD, levels of inflammatory mediators and erythropoietin are elevated compared to nonanemic controls.

Anemia and Survival in Chronic Obstructive Pulmonary Disease: A Dichotomous rather than a Continuous Predictor

Background: Chronic obstructive pulmonary disease (COPD) is a disorder characterized by high mortality. Hemoglobin (Hb) concentration has a prognostic impact on COPD patients receiving long-term oxygen treatment, but its value as an independent predictor of survival among stable COPD outpatients has not been fully clarified by previous studies. Objectives: To investigate the potential association between anemia and survival in a cohort of stable COPD outpatients. Methods: A cohort of stable COPD patients, who had had their first spirometry, blood count and serum chemistry profile done between October 1999 and November 2010 were retrospectively analyzed. Patients with heart failure, renal impairment, malignancy, recent hemorrhage and other causes of anemia were excluded. Variables that were found to be univariately associated with survival entered a multivariate stepwise Cox regression analysis model, to allow independent predictors of survival to be identified. Results: Of 294 patients (67.9 ± 9.8 years old, 64.6% male) 15.6% were anemic (Hb <13 g/dl). The median survival differed significantly between anemic [68.7 (18.1–91.5) months] and nonanemic [79.8 (57.5–98.4) months, p = 0.035] individuals. Independent predictors of mortality in the total population were anemia [hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.06–3.29], age (HR 1.08, 95% CI 1.04–1.12) and forced expiratory volume in 1 s (FEV1) % predicted (HR 0.94, 95% CI 0.92–0.97); the Hb concentration was neither univariately nor multivariately associated with mortality. Conclusion: This is the first study to indicate that anemia (but not the Hb value) is independently associated with survival in stable COPD outpatients. It would be better to treat this as a categorical variable in future scoring systems.

Haemarthrosis after superwarfarin poisoning

Introduction:  Superwarfarins are widely used as rodenticides. They are similar to warfarin, but they are more potent and act longer. In case of poisoning, they cause severe bleeding, usually from multiple sites.

The Impact of Pulmonary Arterial Pressure on Exercise Capacity in Mild-to-Moderate Cystic Fibrosis: A Case Control Study

Background. Pulmonary hypertension (PH) is an often complication of severe cystic fibrosis (CF); however, data on the presence and impact of pulmonary vasculopathy in adult CF patients with milder disease, is very limited. Aim. To investigate, for the first time, the impact of systolic pulmonary arterial pressure (PASP) on maximal exercise capacity in adults with mild-to-moderate cystic fibrosis, without PH at rest. Methods. This is a Case Control study. Seventeen adults with mild-to-moderate CF, without PH at rest (cases) and 10 healthy, nonsmoking, age, and height matched controls were studied. All subjects underwent maximal cardiopulmonary exercise testing and echocardiography before and within 1 minute after stopping exercise. Results. Exercise ventilation parameters were similar in the two groups; however, cases, compared to controls, had higher postexercise PASP and decreased exercise capacity, established with lower peak work rate, peak O2 uptake, anaerobic threshold, and peak O2 pulse. Furthermore, the change in PASP values before and after exercise was strongly correlated to the parameters of exercise capacity among cases but not among controls. Conclusions. CF adults with mild-to-moderate disease should be screened for the presence of pulmonary vasculopathy, since the elevation of PASP during exercise might contribute to impaired exercise capacity.

Should we routinely screen patients with idiopathic pulmonary fibrosis for nocturnal hypoxemia

Dear Editor, An increased incidence of sleep-disordered breathing in patients with idiopathic pulmonary fibrosis (IPF) has been reported in recently published studies [1–3]. Sleep-related oxygen desaturation seems to represent a common, usually undertreated disorder in these patients [4]. Nocturnal hypoxemia theoretically might aggravate vasoconstriction and vascular remodeling in pulmonary circulation. Pulmonary hypertension (PH) is a common complication of IPF with a reported incidence ranging from 32 to 85 % [5]. The development of PH during the course of the disease has a negative impact on functional status and quality of life of IPF patients and is associated with a poor survival [6, 7]. Currently, there is no specific therapy for PH associated with IPF, and the published experience with specific PH drug therapy is disappointing. The pathogenesis of PH in IPF is incompletely understood. Hypoxic pulmonary vasoconstriction leading to permanent medial hypertrophy is a wellrecognized mechanism of PH in chronic lung disease. Patients with IPF often demonstrate hypoxemia, commonly with minimal exercise and even at rest at advanced stages of the disease. However, the role of nocturnal hypoxemia in the development of PH in IPF patients has not been studied thoroughly. Given this background, we sought to determine the potential correlation between nocturnal hypoxemia and PH in a cohort of IPF patients. Thirty-three consecutive IPF patients (26 male), mean age 69±8.7 years, referred for evaluation in the respiratory failure unit, were prospectively studied. Diagnosis of IPF was established according to the American Thoracic Society/European Respiratory Society criteria [8]. All patients underwent pulmonary function tests (PFTs), arterial blood gases measurement at room air, 6-min walk test with recording of O2 saturation (SpO2) by noninvasive pulse oximetry, and a limited sleep study with recording of finger pulse oximetry using a portable diagnostic system (Embletta; Medcare Flaga, Reykjavik, Iceland). During the sleep study, none of the patients was under supplemental oxygen therapy. Pulmonary function assessment was performed by spirometry (MasterScreen PFT; Jaeger, Höchberg, Germany). Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), DLCO, and carbon monoxide transfer coefficient (KCO, in percent) were measured. A transthoracic echocardiographic study was performed within 1 week of the initial evaluation of the patients. Resting systolic pulmonary arterial pressure (sPAP) was estimated by calculating the maximal velocity of the tricuspid regurgitant jet, applying the Bernoulli equation and then adding to this value an estimated right atrial pressure, based on both the size of the inferior vena cava and the change in diameter of this vessel during respiration. PH was defined as sPAP of >36 mmHg. The patients were clinically stable and continued to receive the same medical treatment throughout the study. All data are presented as means±1 SD. The Pearson’s G. Pitsiou (*) :V. Bagalas :A. Boutou : I. Stanopoulos : P. Argyropoulou-Pataka Respiratory Failure Unit, Gen. Hospital “G. Papanikolaou”, Aristotle University of Thessaloniki, Exohi, Thessaloniki 57010, Greece e-mail: gpitsiou@yahoo.gr

Phenotyping Exercise Limitation in Systemic Sclerosis: The Use of Cardiopulmonary Exercise Testing

Background: Exercise impairment is a common symptom of systemic sclerosis (SSc), a disorder which is frequently complicated by cardiopulmonary involvement. Objectives: This studys aims were: (a) to define the prevalence and the potential causes of limited exercise capacity and (b) to study potential differences in clinical, radiological and functional characteristics and blood serology among SSc patients with exercise limitation of different etiology. Methods: Prospectively collected data on SSc patients who had conducted full lung function testing, blood serology, thorax high-resolution computed tomography, Doppler echocardiogram and a maximal cardiopulmonary exercise testing (CPET) were retrospectively analyzed. Using a CPET algorithm, patients were characterized as having normal or subnormal exercise capacity (N), respiratory limitation (RL), left ventricular dysfunction (LVD) or pulmonary vasculopathy (PV). Group comparisons were conducted using either one-way ANOVA or the Kruskal-Wallis test. A p value <0.05 was considered significant. Results: The study population consisted of 78 patients (53.7 ± 13.7 years old; 10.3% male). PV was present in 32.1%, LVD in 25.6% and RL in 10.2%, while 32.1% of the patients constituted the N group. The presence of antisclero-70 antibodies, low anaerobic threshold and low peak exercise capacity measures could discriminate LVD from the other groups. Low end-tidal carbon dioxide pressure and its change from rest to anaerobic threshold could discriminate between the PV, LVD and N groups, while respiratory restriction along with ventilatory inefficiency indices could differentiate the RL group from the rest. Conclusions: The combined evaluation of CPET gas exchange patterns with baseline measurements could discriminate the causes of exercise limitation among SSc patients.

Sarcoidosis-associated pulmonary hypertension: a role for endothelin receptor antagonists?

Data on the treatment of sarcoidosis-associated pulmonary hypertension are scarce, while the variety of underlying pathophysiologic mechanisms are a major limitation in the implementation of a universal therapy. We report a 47-year-old male patient who presented with stage II sarcoidosis and associated severe pulmonary hypertension. Corticosteroid treatment resolved parenchymal lesions of the lung while vascular involvement did not respond, with the patient remaining in poor functional status. Addition of bosentan, a dual endothelin receptor antagonist, resulted in marked improvement in functional class and exercise capacity of the patient, allowing gradual tapering of steroids.

Successful Up-front Combination Therapy in a Patient With Idiopathic Pulmonary Hypertension and Patent Foramen Ovale: An Alternative to Epoprostenol Therapy?

Pulmonary arterial hypertension (PAH) is a life-threatening disease of the pulmonary arterioles, which, in the absence of effective therapy, progresses rapidly to right heart failure and death. Opening of a patent foramen ovale (PFO) is common in patients with severe pulmonary hypertension (PH), resulting in resistive hypoxemia. We report the case of a 40-year-old woman with idiopathic pulmonary hypertension (iPAH) in New York Heart Association (NYHA) class III to IV, who was admitted in the intensive care unit with hemodynamic compromise and severe hypoxemia due to right-to-left shunt throughout a PFO. Combination therapy initially with inhaled iloprost and sildenafil, and then addition of an endothelin A receptor-selective antagonist (sitaxsentan), resulted in impressive improvement in oxygenation with reversal of the right-to-left shunt and marked improvement in functional class of the patient.