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The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Nasal high-flow provides a stable oxygenation in acute hypoxemic respiratory failure, modifies breathing patterns, reduces work of breathing and can decrease hypercapnia. Thereby NHF provides more features than low-flow oxygen and acts as a ventilatory support device. Different studies show benefits of NHF compared to NIV. For these reasons we will discuss the capabilities of NHF and NIV in selected settings., Competing Interests: J. B. erhielt Vortragshonorare, Geräte und Reiseunterstützung der TNI medical AG.H. W. erhielt Vortragshonorare und Geräte der TNI medical AG., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Despite the encouraging results of noninvasive ventilation (NIV) in chronic hypercapnic COPD patients, it is also evident that some patients do not tolerate NIV or do not benefit from it. We conducted a study in which COPD patients with stable, chronic hypercapnia were treated with NIV and nasal high-flow (NHF) to compare effectiveness., Methods: In a multi-centered, randomized, controlled, cross-over design, patients received 6 weeks of NHF ventilation followed by 6 weeks of NIV ventilation or vice-versa (TIBICO) between 2011 and 2016. COPD patients with stable daytime hypercapnia (pCO 2 ≥50 mmHg) were recruited from 13 German centers. The primary endpoint was pCO 2 changes from baseline blood gas, lung function, quality of life (QoL), the 6 min walking test, and duration of device use were secondary endpoints., Results: A total of 102 patients (mean±SD) age 65.3±9.3 years, 61% females, body mass index 23.1±4.8 kg/m 2 , 90% GOLD D, pCO 2 56.5±5.4 mmHg were randomized. PCO 2 levels decreased by 4.7% (n=94; full analysis set; 95% CI 1.8-7.5, P =0.002) using NHF and 7.1% (95% CI 4.1-10.1, P <0.001) from baseline using NIV (indistinguishable to intention-to-treat analysis). The difference of pCO 2 changes between the two devices was -1.4 mmHg (95% CI -3.1-0.4, P =0.12). Both devices had positive impact on blood gases and respiratory scores (St. George's Respiratory Questionnaire, Severe Respiratory Insufficiency Questionnaire)., Conclusions: NHF may constitute an alternative to NIV in COPD patients with stable chronic hypercapnia, eg, those not tolerating or rejecting NIV with respect to pCO 2 reduction and improvement in QoL., Competing Interests: Dr. Bräunlich reports grants and non-financial support from TNI Medical AG during the conduct of the study; and grants, personal fees and non-financial support from TNI Medical AG and personal fees from Fisher&Paykel, outside the submitted work. Prof. Kähler reports non-financial support from TNI Medical AG. Prof. Randerath reports grants from Heinen und Löwenstein, Weinmann, Philips Respironics, and Inspire, outside the submitted work. Prof. Wirtz reports personal fees and non-financial support from TNI Medical AG, during the conduct of the study. All other authors have nothing to disclose.

Introduction: Nasal highflow (NHF) has a growing evidence in treatment of hypoxemic respiratory failure. There are preliminary data available about use in acute and chronic type-II-respiratory failure. Unfortunately underlying mechanisms of NHF are not well understood. Increase in airway pressure seems too small to explain the observed reduction in hypercapnia. Most interesting effects are wash-out of upper airways and reduction of functional dead space. There are no data available about a wash-out of lower airways., Methods: We established a sheep lung model to evaluate CO 2 -wash-out in lower airways. Therefore we placed measuring and insufflation catheter in maximal expanded lung. The lung was not ventilated in order to minimize influence of CO 2 rebreathing and increase in airway pressure. Airway pressure and CO 2 values were measured in lower airways and in tracheal space., Results: CO 2 was decreased by NHF in lower airways and in tracheal space. Changes in CO 2 were flow dependent. There was also an increase in airway pressure in these settings., Conclusions: NHF is able to decrease CO 2 in lower airways in a flow-dependent manner. This effect is independent of an increase in airway pressure and CO 2 -rebreathing. So wash-out is an important reason for efficiency of NHF in decreasing hypercapnia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n = 109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ≥25 mm Hg (P = 0.013, P = 0.006, P = 0.049, P = 0.002, P = 0.68, respectively) and with PVR ≥480 dyn·s/cm (P < 0.001, P = 0.045, P < 0.001, P < 0.001, P = 0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r = 0.55, r = 0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease., Competing Interests: The authors report no potential conflict of interest relevant to this article.

Background: Nasal highflow (NHF) provides a warmed and humidified air stream up to 60 L/min. Recent data demonstrated a positive effect in patients with acute hypoxemic respiratory failure, especially when caused by pneumonia. Preliminary data show a decrease in hypercapnia in patients with COPD. Therefore, NHF should be evaluated as a new ventilatory support device. This study was conducted to assess the impact of different flow rates on ventilatory parameters in patients with COPD., Materials and Methods: This interventional clinical study was performed with patients suffering from severe COPD. The aim was to characterize flow-dependent changes in mean airway pressure, breathing volumes, breathing frequency, and decrease in partial pressure of CO2 (pCO2). Mean airway pressure was measured in the nasopharyngeal space (19 patients). To evaluate breathing volumes, we used a polysomnographic device (18 patients). All patients received 20 L/min, 30 L/min, 40 L/min, and 50 L/min and - to illustrate the effects - nasal continuous positive airway pressure and nasal bilevel positive airway pressure. Capillary blood gas analyses were performed in 54 patients with hypercapnic COPD before and two hours after the use of NHF. We compared the extent of decrease in pCO2 when using 20 L/min and 30 L/min. Additionally, comfort and dyspnea during the use of NHF were surveyed., Results: NHF resulted in a minor flow dependent increase in mean airway pressure. Tidal volume increased, and breathing rate decreased. The calculated minute volume decreased under NHF breathing. In spite of this fact, hypercapnia decreased with increasing flow (20 L/min vs 30 L/min). Additionally, an improvement in dyspnea was observed. The rapid shallow breathing index shows a decrease when using NHF., Conclusion: NHF leads to a flow-dependent reduction in pCO2. This is most likely achieved by a washout of the respiratory tract and a functional reduction in dead space. In summary, NHF enhances effectiveness of breathing in patients with COPD, reduces pCO2, the work of breathing, and rapid shallow breathing index as an indicator of respiratory work load.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. These guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the use of these drugs in patients with chronic lung disease and PH is not recommended. This recommendation, however, is not always in agreement with medical needs as physicians feel sometimes inclined to also treat other forms of pulmonary hypertension which may affect the quality of life and survival of these patients in a similar manner as in PAH. In June 2010, a consensus conference was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology (DGK, DGP and DGPK). To this end, a number of working groups were initiated, one of which was specifically dedicated to the diagnosis and treatment of PH due to chronic lung disease. This manuscript describes in detail the results and recommendations of this working group which were last updated in October 2011., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The lung is a dynamic organ that is subjected to mechanical forces throughout development and adult life. This review article addresses the types of mechanical forces in the lung and their effects on development and normal lung functions. The effects of mechanical forces on the various different cell types of the lung are discussed, as are the mechanisms underlying mechanotransduction.