Stefan Scheidl

Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review

According to current guidelines, pulmonary arterial hypertension (PAH) is diagnosed when mean pulmonary arterial pressure (P̄pa) exceeds 25 mmHg at rest or 30 mmHg during exercise. Issues that remain unclear are the classification of P̄pa values <25mmHg and whether P̄pa >30 mmHg during exercise is always pathological. We performed a comprehensive literature review and analysed all accessible data obtained by right heart catheter studies from healthy individuals to determine normal P̄pa at rest and during exercise. Data on 1,187 individuals from 47 studies in 13 countries were included. Data were stratified for sex, age, geographical origin, body position and exercise level. P̄pa at rest was 14.0±3.3 mmHg and this value was independent of sex and ethnicity. Resting P̄pa was slightly influenced by posture (supine 14.0±3.3 mmHg, upright 13.6±3.1 mmHg) and age (<30 yrs: 12.8± 3.1mmHg; 30–50 yrs: 12.9±3.0 mmHg; ≥50 yrs: 14.7±4.0 mmHg). P̄pa during exercise was dependent on exercise level and age. During mild exercise, P̄pa was 19.4±4.8 mmHg in subjects aged <50 yrs compared with 29.4±8.4 mmHg in subjects ≥50 yrs (p<0.001). In conclusion, while P̄pa at rest is virtually independent of age and rarely exceeds 20 mmHg, exercise P̄pa is age-related and frequently exceeds 30 mmHg, especially in elderly individuals, which makes it difficult to define normal P̄pa values during exercise.

Borderline pulmonary arterial pressure is associated with decreased exercise capacity in scleroderma.

RATIONALE Pulmonary arterial hypertension is associated with impaired exercise capacity and decreased survival in patients with scleroderma. Randomized controlled studies showed significant benefit of targeted therapies in patients with a resting mean pulmonary arterial pressure (MPAP) greater than 25 mm Hg. The clinical relevance of pulmonary arterial pressure values in the upper normal range is unknown. OBJECTIVES To examine the clinical relevance of pulmonary arterial pressure in scleroderma patients. METHODS After a noninvasive screening program, 29 patients with systemic sclerosis without significant lung fibrosis and without known pulmonary arterial hypertension underwent right heart catheterization and simultaneous cardiopulmonary exercise test. A six-minute walk distance (6MWD) was determined within 48 hours. MEASUREMENTS AND MAIN RESULTS A resting MPAP above the median (17 mm Hg) was associated with decreased 6MWD (396 +/- 71 vs. 488 +/- 76 m; P < 0.005) and peak Vo(2) (76 +/- 11% vs. 90 +/- 24%; P = 0.05). Resting pulmonary vascular resistance was inversely correlated with 6MWD (r = 0.45; P < 0.05). At 25 and 50W, MPAP above the median (23 and 28 mm Hg) was associated with decreased 6MWD (P < 0.005; P < 0.0005). At peak exercise, MPAP showed no association with 6MWD or peak Vo(2); however, cardiac index was positively (r = 0.45; P < 0.05) and pulmonary vascular resistance was negatively correlated with 6MWD (r = -0.38; P < 0.05). CONCLUSIONS MPAP and resistance in the upper normal range at rest and moderate exercise are associated with decreased exercise capacity and may indicate early pulmonary vasculopathy in patients with systemic sclerosis. Investigations on the prognostic and therapeutic implications of such borderline findings are warranted. Clinical trial registered with http://www.clinicaltrials.gov (NCT00609349).

Assessment of Pulmonary Arterial Pressure During Exercise in Collagen Vascular Disease : Echocardiography vs Right-Sided Heart Catheterization

BACKGROUND This study compared the results of exercise Doppler echocardiography (EDE) with right-sided heart catheterization (RHC) and evaluated the combination of EDE and cardiopulmonary exercise testing (CPET) as a screening method for early pulmonary vasculopathy in patients with connective tissue disease. METHODS Patients (N = 52) with connective tissue disease (predominantly systemic sclerosis) and without known pulmonary arterial hypertension underwent both EDE and CPET. If systolic pulmonary arterial pressure (SPAP) was > 40 mm Hg during exercise or peak oxygen uptake (Vo(2)) was < 75% predicted, RHC was suggested. RESULTS EDE showed an SPAP > 40 mm Hg during exercise in 26/52 patients. Additionally, CPET showed a peak Vo(2) < 75% predicted in 10/26 patients with SPAP <or= 40 mm Hg upon exercise. Accordingly, RHC was suggested to 36 patients. RHC was performed in 28 of these patients, revealing SPAP > 40 mm Hg in 25 patients (n = 1 at rest, n = 24 during exercise). SPAP values assessed by EDE showed no significant difference vs RHC at rest, 25 W, 50 W, and maximal exercise (difference [95% CI]: 0.3 [-2.7; 3.2], -1.3 [-7.1; 4.4], 0.9 [-7.7; 5.9], and -5.6 [-13.5; 2.2] mm Hg). Eight patients with exercise SPAP > 40 mm Hg had an exercise pulmonary arterial wedge pressure > 20 mm Hg, suggesting exercise-induced left ventricular diastolic dysfunction not detectable by EDE. CONCLUSIONS EDE appears to be a reasonable noninvasive method to detect SPAP increase during exercise in connective tissue disease. In combination with CPET, it may be a useful screening tool for early pulmonary vasculopathy, although RHC remains the gold standard for hemodynamic assessment. TRIAL REGISTRATION clinicaltrials.gov; Identifier: NCT00609349 (Early Recognition of Pulmonary Arterial Hypertension).

Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure

OBJECTIVE Borderline pulmonary arterial hypertension (PAH), characterized by a marked exercise-induced increase in pulmonary artery pressure (PAP) with normal resting values, may precede overt PAH in systemic sclerosis (SSc). We undertook the present study to investigate whether PAH treatment is safe in these patients and might attenuate hemodynamic progression. METHODS SSc patients with borderline PAH underwent right heart catheterization at baseline, after a 12-month observation period, and subsequently after 6 months of bosentan therapy. Changes in mean PAP at 50W during the observation period versus during therapy were compared. RESULTS Ten patients completed the study. Mean PAP at rest, at 50W, and during maximal exercise increased significantly during the observation period (mean ± SD increases of 2.5 ± 3.0 mm Hg [P = 0.03], 4.0 ± 2.9 mm Hg [P = 0.002], and 6.8 ± 4.1 mm Hg [P = 0.0005], respectively) and tended to decrease during the treatment period (decreases of 2.5 ± 3.9 mm Hg [P = 0.07], 1.5 ± 4.5 mm Hg [P = 0.32], and 1.8 ± 7.0 mm Hg [P = 0.43], respectively). The changes during the observation period versus the therapy period were significantly different (P = 0.03 at rest, P = 0.01 at 50W [primary end point], and P = 0.02 during maximal exercise). The changes in resting pulmonary vascular resistance were also significantly different during the observation period (increase of 8 ± 25 dynes · seconds · cm(-5) ) versus during the therapy period (decrease of 45 ± 22 dynes · seconds · cm(-5) ) (P < 0.0005). Changes in resting pulmonary arterial wedge pressure were not significantly different between the observation period and the treatment period, despite the significant increase during the observation period (2.6 ± 2.5 mm Hg [P = 0.01]). No relevant adverse effects were reported. CONCLUSION In SSc patients with borderline abnormal pulmonary hemodynamics, resting and exercise PAP may increase significantly within 1 year of observation. Bosentan might be safe and effective to attenuate these changes. Randomized controlled trials are warranted to confirm the exploratory findings of this hypothesis-generating pilot study.

Diagnosis of CTEPH versus IPAH using capillary to end-tidal carbon dioxide gradients.

Chronic thromboembolic pulmonary hypertension (CTEPH) represents an important differential diagnosis to idiopathic pulmonary arterial hypertension (IPAH). We hypothesised that the capillary to end-tidal carbon dioxide gradient at rest and during exercise might help differentiate CTEPH from IPAH. Patients who presented with unequivocal IPAH or CTEPH according to ventilation/perfusion scanning, pulmonary angiography, computed tomography and right heart catheterisation were included in this retrospective study and compared with healthy controls. 21 IPAH patients and 16 CTEPH patients fulfilled the inclusion criteria. Haemodynamics and peak oxygen uptake were comparable, but respiratory rates at rest and during exercise were significantly higher in CTEPH than in IPAH. End-tidal carbon dioxide was significantly lower in CTEPH versus IPAH at rest and during exercise, while capillary carbon dioxide values were similar. Correspondingly, capillary to end-tidal carbon dioxide gradients were significantly increased in CTEPH versus IPAH at rest and during exercise (median (range) 8.6 (3.0–13.7) versus 4.4 (0.9–9.0) (p<0.001) and 9.3 (3.3–13.1) versus 4.1 (0.0–8.8) mmHg (p<0.001), respectively). Although these values were closer to normal in IPAH they were still significantly elevated compared with healthy controls (2.3 (-4.8–8.1) and -1.9 (-5.7–6.2) mmHg, respectively). Capillary to end-tidal carbon dioxide gradients may help to distinguish CTEPH from IPAH based on resting and exercise values.

Intimal Sarcoma of the Pulmonary Valve

Pulmonary artery intimal sarcoma is a rare tumor of the cardiovascular system. Intimal sarcoma of the pulmonary valve itself has not been described. Embolization into pulmonary arteries originating from the pulmonary valve intimal sarcoma can mimic chronic thromboembolic pulmonary hypertension and mislead the diagnosis. We present and discuss a patient initially diagnosed as chronic thromboembolic pulmonary hypertension, treated by pulmonary endarterectomy. After 24 months, a tumor of the pulmonary valve was detected by echocardiography. The patient underwent removal and replacement of the pulmonary valve. Histology revealed pulmonary valve intimal sarcoma.

Pulmonary histoplasmosis in three Austrian travelers after a journey to Mexico.

Three Austrian travelers (a 37-year-old woman, a 47-year-old woman and a 47-year-old man) presented with fever, dyspnea, thoracodynia, cephalea, arthralgia and fatigue 4 weeks after visiting a bat cave in Mexico. Computed tomography of the lungs showed bilateral nodular infiltrates in all three patients and enlarged mediastinal lymphnodes in two patients. In all patients, specific IgM antibodies against Histoplasma capsulatum could be detected. After treatment with itraconazole 200 mg qd orally for 2 months, the patients had no further complaints and the pulmonary infiltrates had resolved.

A 55-year-old craftsman with dyspnea and clubbing: a case report

IntroductionClubbing is very uncommon in respiratory bronchiolitis-associated interstitial lung disease, and primarily raises the suspicion of idiopathic pulmonary fibrosis in a patient presenting with diffuse parenchymal lung disease. If idiopathic pulmonary fibrosis can be excluded, clubbing should raise the suspicion of an occult tumour.Case presentationWe describe a heavy smoker presenting with dyspnea and severe clubbing. Surgical lung biopsy revealed the histologic diagnosis of respiratory bronchiolitis-associated interstitial lung disease. Respiratory bronchiolitis-associated interstitial lung disease is a distinct clinicopathologic entity within idiopathic interstitial pneumonia patients described almost exclusively in cigarette smokers. The disease is associated with a good prognosis and mild symptoms but not with clubbing. After smoking cessation the radiologic findings of interstitial lung disease improved in parallel with improvement in lung function and gas exchange. However, a central squamous cell carcinoma was detected in the follow-up.ConclusionIn this case, clubbing was most probably caused by the occult tumor rather than by respiratory bronchiolitis-associated interstitial lung disease.

Clinical Manifestations of Respiratory Bronchiolitis as an Incidental Finding in Surgical Lung Biopsies: A Retrospective Analysis of a Large Austrian Registry

Background: While respiratory bronchiolitis (RB) is a frequent histopathological finding in smokers lungs, RB-associated interstitial lung disease (RB-ILD) remains a rare disease. Objectives: We analyzed how the histological finding of RB was associated with clinical information in a series of 684 consecutive surgical lung biopsies. Methods: Retrospective analysis with delineation of clinical manifestations, smoking habits, pulmonary function test, and blood gas analysis in patients with RB in surgical lung biopsy. In 240 of these biopsies, RB was diagnosed, and in 146 of these cases a full clinical dataset was available. Results: The final diagnosis of these 146 patients was consistent with RB-ILD (n = 18), pulmonary Langerhans cell histiocytosis (n = 7), various ILD (n = 9), spontaneous pneumothorax (n = 43), traumatic pneumothorax (n = 5), lung cancer (n = 41), various benign lung tumors (n = 8), and chronic pulmonary effusion (n = 15). Smoking history was positive in 93% of patients, 72% revealed centrilobular emphysema in their biopsy, and 58% described dyspnea as the main symptom. Amongst these diagnoses there were significant differences in age and smoking habits, but only small distinctions in pulmonary function test and blood gas analysis. Out of the patients with RB-ILD, 17% developed lung cancer in the later course. Conclusion: RB is strongly related to smoking, emphysema, and dyspnea and frequently associated with lung cancer. RB-ILD is a rare disease that may represent a considerable risk for lung cancer. Pulmonary function testing and blood gas analysis do not differ between RB-associated diseases. The finding of RB should prompt further diagnostic workup, and in case of RB-ILD, entail regular screening for lung cancer.

Whole-Body Lung Function Test–Derived Outcome Predictors in Allogenic Stem Cell Transplantation

Despite clinical advances, late onset pulmonary complications in adult recipients of allogenic stem cell transplantation are a major cause of morbidity and mortality. Reported incidence and risk factors in the literature vary broadly and are partly contradictory. Identification of pretransplant factors associated with major complications would be helpful to define individual treatment strategies and early initiation of preventive measures. To evaluate incidence and risk factors of late onset noninfectious pulmonary complications, with special regard to small airways disease (SAD) and bronchiolitis obliterans syndrome (BOS), indicating graft-versus-host disease, following myeloablative versus nonmyeloablative allogenic stem cell transplantation. We reviewed the clinical records and assessed the course of lung function and pulmonary complications in adults who underwent allogenic stem cell transplantation for hematological malignancies between 1999 and 2015 using nonmyeloablative (n = 179) or myeloablative (n = 130) conditioning at the Division of Hematology of the Medical University of Graz. All patients underwent body plethysmography pulmonary function test (PFT), diffusion capacity for carbon monoxide, and arterial blood gas analysis before and repeatedly after transplant. SAD was defined as maximal expiratory flow at 50% and 25% of forced vital capacity <70% predicted. Ventilatory disorders and gas transfer abnormalities were common before and after allogenic stem cell transplantation, independent of conditioning regimen. SAD was common in the nonmyeloablative (34%) and myeloablative (29%) groups. The 100-day post-transplant mortality was significantly associated with reduced pretransplant total lung capacity <80%. Mortality 100 days post-transplant was significantly associated with pretransplant SAD and a pretransplant smoking history. In this subset, a smoking history was independently associated with increased mortality, with a 5-year mortality of 45% compared with 26% in never-smokers. Pretransplant SAD was not predictive for the later development of BOS. Smoking history, pretransplant restrictive PFT, and pre-existing SAD are important risk factors for death following allogenic stem cell transplantation. However, pretransplant SAD is not a predictor of long-term complications, including BOS.