Reindert P. van Steenwijk

Pulmonary Endarterectomy Improves Dyspnea by the Relief of Dead Space Ventilation

BACKGROUND In chronic thromboembolic pulmonary hypertension (CTEPH), dyspnea is considered to be related to increased dead space ventilation caused by vascular obstruction. Pulmonary endarterectomy releases the thromboembolic obstruction, thereby improving regional pulmonary blood flow. We hypothesized that pulmonary endarterectomy reduces dead space ventilation and that this reduction contributes to attenuation of dyspnea symptoms. METHODS In this follow-up study we assessed dead space ventilation, hemodynamic severity of disease, and symptomatic dyspnea in 54 consecutive CTEPH patients, before and 1 year after pulmonary endarterectomy. Dead space ventilation was calculated using the Bohr-Enghoff equation. Dyspnea was assessed by Borg scores and the New York Heart Association functional classification. RESULTS Preoperatively, dead space ventilation was increased (0.40 +/- 0.07) and correlated with severity of disease (mean pulmonary artery pressure: r = 0.49, p < 0.001; total pulmonary resistance: r = 0.53, p < 0.001), and resting (r = 0.35, p < 0.05) and post-exercise Borg dyspnea scores (r = 0.44, p < 0.01). Postoperatively, dead space ventilation (0.33 +/- 0.08, p < 0.001) and dyspnea symptoms decreased significantly. Changes in symptomatic dyspnea were independently associated with changes in pulmonary hemodynamics and absolute dead space. CONCLUSIONS Dead space ventilation in CTEPH is increased and correlates significantly with hemodynamic severity of disease and dyspnea symptoms. Pulmonary endarterectomy decreases dead space ventilation. The induced change in dead space upon surgical removal of chronic thromboembolism contributes to the postoperative recovery of symptomatic dyspnea.

Effects of treatment of obstructive sleep apnea on circadian hemodynamics

INTRODUCTION The role of obstructive sleep apnea syndrome (OSAS) in the etiology of daytime hypertension is still an issue of debate, which is fed by the high prevalence of the syndrome in hypertensive patients. In this study the anti-hypertensive effect of short-term treatment of obstructive sleep apnea with nasal continuous positive airway pressure (nCPAP) was assessed. PATIENTS AND METHODS In eight patients with documented OSAS (mean apnea index 62 apneas/h), two 24-h continuous finger blood pressure registrations (Portapres) were performed. At baseline and after 3 weeks of treatment with nCPAP. Ten hypertensive control subjects were studied. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were assessed by pulse contour analysis. RESULTS Hemodynamics were highly reproducible in the controls. nCPAP therapy improved apnea-activity in all OSAS patients. This was associated with a reduction of nighttime systolic (SBP), mean arterial (MAP) and diastolic blood pressure (DBP). Treatment also reduced daytime MAP by -11 mm Hg (ranging from -27 to 1; P < 0.05), and DBP by -7 mm Hg (-24 to 3; P < 0.05). CO was significantly increased in daytime by 9% (-4 to 25; P < 0.05), whereas TPR was reduced by -15% (-34 to 3; P < 0.05). CONCLUSIONS Treatment of OSAS caused a reduction in daytime MAP and DBP, associated with a reduction of vascular resistance. These findings are consistent with the hypothesis of a reduced sympathetic outflow at night after therapy of obstructive sleep apnea, carrying over to the day.

Longitudinal Follow-Up of Six-Minute Walk Distance After Pulmonary Endarterectomy

BACKGROUND The 6-minute walk test is a useful tool to assess functional outcome after pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension. However, little is known about the longitudinal dynamics in functional improvement. We performed a longitudinal follow-up of 6-minute walk distance, New York Heart Association functional class, and echocardiography after PEA. METHODS We studied 71 patients with chronic thromboembolic pulmonary hypertension who underwent PEA. A 6-minute walk test and echocardiography were performed before PEA, at 3 months after, and at annual follow-up. At the time of this report, 52 patients had returned for 2-year follow-up, 32 for 3-year follow-up, 23 for 4-year follow-up, and 11 for 5-year follow-up. RESULTS Preoperatively, the 6-minute walk distance (6-MWD) correlated with hemodynamic severity of disease (mean pulmonary artery pressure: r = -0.55, p < 0.001); total pulmonary resistance: r = -0.59, p < 0.001) After PEA, 6-MWD increased from 440 ± 109 to 524 ± 83 meters at 1 year (n = 71, p < 0.001). Further improvement was observed from 523 ± 87 meters at 1 year to 536 ± 91 meters at 2 years (n = 52, p < 0.012). After 2 years, no further improvement was observed. At 1 year, the change in 6-MWD from baseline correlated significantly with the change observed in pulmonary hemodynamics. Changes in 6-MWD and hemodynamics were more pronounced in patients with residual pulmonary hypertension after PEA, despite the worse absolute outcome. CONCLUSIONS In patients with chronic thromboembolic pulmonary hypertension, 6-MWD showed a gradual improvement up to 2 years after PEA. Patients with residual pulmonary hypertension benefited most from treatment, despite the worse absolute outcome.

Fibrotic idiopathic interstitial pneumonias: Mortality is linked to a decline in gas transfer

Background and objective:  Baseline clinical and physiological features and changes in these parameters over time are known predictors of survival in patients with fibrotic idiopathic interstitial pneumonia (IIP). Pulmonary hypertension is common in advanced fibrotic IIP, and has a negative impact on survival. Serial pulmonary function profiles, indicative of increasing vascular impairment in patients with IIP, and in particular, selective reductions in gas transfer, have not been studied previously.

Airway inflammation and mannitol challenge test in COPD

BackgroundEosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled mannitol captures eosinophilia in induced sputum in COPD.MethodsTwenty-eight patients (age 58 ± 7.8 yr, packyears 40 ± 15.5, post-bronchodilator FEV1 77 ± 14.0%predicted, no inhaled steroids ≥4 wks) with mild-moderate COPD (GOLD I-II) completed two randomized visits with hypertonic saline-induced sputum and mannitol challenge (including sputum collection). AHR to mannitol was expressed as response-dose-ratio (RDR) and related to cell counts, ECP, MPO and IL-8 levels in sputum.ResultsThere was a positive correlation between RDR to mannitol and eosinophil numbers (r = 0.47, p = 0.03) and level of IL-8 (r = 0.46, p = 0.04) in hypertonic saline-induced sputum. Furthermore, significant correlations were found between RDR and eosinophil numbers (r = 0.71, p = 0.001), level of ECP (r = 0.72, p = 0.001), IL-8 (r = 0.57, p = 0.015) and MPO (r = 0.64, p = 0.007) in sputum collected after mannitol challenge. ROC-curves showed 60% sensitivity and 100% specificity of RDR for >2.5% eosinophils in mannitol-induced sputum.ConclusionsIn mild-moderate COPD mannitol hyperresponsiveness is associated with biomarkers of airway inflammation. The high specificity of mannitol challenge suggests that the test is particularly suitable to exclude eosinophilic airways inflammation, which may facilitate individualized treatment in COPD.Trial registrationNetherlands Trial Register (NTR): NTR1283

Exercise tolerance, lung function abnormalities, anemia, and cardiothoracic ratio in sickle cell patients.

Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation. Forty‐four consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS‐beta thalassemia) with a median age (interquartile range) of 26 (21–41) years underwent pulmonary function tests, CPET, chest x‐ray, and echocardiography to further characterize exercise limitation in SCD. Peak oxygen uptake (V′O2‐peak), expressing maximum exercise capacity, was decreased in 83% of the studied patients. V′O2‐peak correlated with hemoglobin levels (R = 0.440, P = 0.005), forced vital capacity (FVC) (R = 0.717, P < 0.0001). Cardiothoracic ratio on chest x‐ray inversely correlated with FVC (R = −0.637, P < 0.001). According to criteria for exercise limitation, the patients were limited in exercise capacity due to anemia (n = 17), cardiovascular dysfunction (n = 2), musculoskeletal function (n = 10), pulmonary ventilatory abnormalities (n = 1), pulmonary vascular exercise limitation (n = 1), and poor effort (n = 3). In the present study we demonstrate that anemia is the most important determinant of reduced exercise tolerance observed in SCD patients without signs of pulmonary hypertension. We found a strong correlation between various parameters of lung volume and cardiothoracic ratio and we hypothesize that cardiomegaly and relative small chest size may be important causes of the impairment in pulmonary function, that is, reduced long volumes and diffusion capacity, in SCD. Taking into account anthropomorphic differences between SCD patients and controls could help to interpret lung function studies in SCD better. Am. J. Hematol. 89:819–824, 2014.

Sleep apnea syndrome as extreme condition of the respiratory control system

Control of respiration is hampered by the mechanics of the respiratory system: only once per breath can the respiratory control system adapt to changing input signals (chemoreception) or changing demands like increased muscular work. This implies an inevitable instability of pulmonary capillary Pco2 and Po2, leading to cyclic changes in synchrony with inspiratory and expiratory movements. In addition, chemoreflexes act only after a delay to changes in pulmonary gas tensions due to the circulatory delay from the lungs to the areas of chemoreception. Thus, in spite of the availability of continuous stimuli to chemoreceptors, both the delays of afferent information and the nature of the effector organ can lead to (slower) oscillations in the respiratory control system, with periods of several or more breaths.