Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension ...(PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH.
Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined.
Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9–15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively).
Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes.
Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.
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•Portopulmonary hypertension is a severe complication of portal hypertension.•Therapies targeting pulmonary arterial hypertension improve cardiopulmonary haemodynamics.•Combining these therapies and liver transplantation is associated with excellent long-term outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, ...in particular mitomycin C (MMC), and PVOD has been reported.
What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD?
We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum).
From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mm Hg, a cardiac index of 2.2 (1.5-4) L/(min × m2), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31% (20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P = .10), 6-min walk distance (P = .09), and pulmonary vascular resistance (–4.7 Wood units; P = .052) at reassessment (median delay of 4.8 months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20 months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively.
PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy.
Purpose
Asthma exacerbations are inflammatory events that rarely result in full hospitalization following an ER visit. Unfortunately, certain patients require prolonged support, including occasional ...external lung support through ECMO or ECCOR (with subsequent further exposure to other life‐threatening issues), and some die. In parallel, biologics are revolutionizing severe asthma management, mostly in T2 high patients.
Methods
We extensively reviewed the current unmet needs surrounding ICU‐admitted asthma exacerbations, with a focus on currently available drugs and the underlying biological processes involved. We explored whether currently available T2‐targeting drugs can reasonably be seen as potential players not only for relapse prevention but also as candidate drugs for a faster resolution of such episodes. The patient's perspective was also sought.
Results
About 30% of asthma exacerbations admitted to the ICU do not resolve within five days. Persistent severe airway obstruction despite massive doses of corticosteroids and maximal pharmacologically induced bronchodilation is the main cause of treatment failure. Previous ICU admission is the main risk factor for such episodes and may eventually be considered as a T2 surrogate marker. Fatal asthma cases are hallmarked by poorly steroid‐sensitive T2‐inflammation associated with severe mucus plugging. New, fast‐acting T2‐targeting biologics (already used for preventing asthma exacerbations) have the potential to circumvent steroid sensitivity pathways and decrease mucus plugging. This unmet need was confirmed by patients who reported highly negative, traumatizing experiences.
Conclusions
There is room for improvement in the management of ICU‐admitted severe asthma episodes. Clinical trials assessing how biologics might improve ICU outcomes are direly needed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely ...unknown characteristics and mechanisms.
Methods
We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network.
Results
Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4–49) years and the median delay between CVID and PH diagnosis was 12 (0–30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease.
Conclusion
PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Immune checkpoint inhibitors (ICI) restore immune response against cancer cells that can lead to immune-related adverse effects. While cardiovascular immune-related adverse effects are known to be ...associated with checkpoint inhibitors, recent case reports have raised concerns about the potential association with pulmonary hypertension (PH). By using the global pharmacovigilance database VigiBase, we investigated the onset of PH associated with ICI and propose a comprehensive description of the 42 cases of PH reported with ICI recorded in this database. Through this study and review of the cases published in the literature, we discuss the possible link between PH and ICI in the context of cancer in order to better understand this rare but potentially fatal event.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Chest computed tomography may be considered to look for disease activity in patients with tuberculosis.•In patients with positive interferon-γ release assay (IGRA), CT better identifies active ...tuberculosis than quantitative IGRA testing.•“Tree-in-bud” pattern, consolidation and non-calcified pulmonary nodules are CT features associated with active tuberculosis.
The purpose of this study was to evaluate the capabilities of chest computed tomography (CT) in distinguishing between active and latent tuberculosis in patients positive for interferon-gamma release assay (IGRA) testing, and to compare the performance of CT with that of quantitative IGRA testing in a low incidence setting.
Patients with latent or active tuberculosis define by an IGRA positive test were retrospectively recruited. Sensitivity, specificity and accuracy were determined for CT variables and quantitative IGRA results. Final diagnosis of active tuberculosis was based on clinical data and microbiological culture. Univariable and multivariable analyses were performed using logistic regression model to identify CT variables associated with the diagnosis of active tuberculosis.
A total of 92 patients with positive IGRA results who underwent CT examination were included. There were 54 men and 38 women with a mean age of 53.5±18 (SD) years (range: 40–68 years). Of them, 22 patients (24%) had positive Mycobacterium tuberculosis culture and 70 (76%) had latent tuberculosis. Among CT variables, consolidation had the greatest sensitivity (77%; 95%CI: 60–95%) and “tree-in-bud” the greatest specificity (97%; 95% CI: 93–100%) for the diagnosis of active tuberculosis. At univariable analysis “tree-in-bud”, splenic calcification and non-calcified lung nodules were the significant variables independently associated with active tuberculosis. At multivariable analysis, the adjusted odds ratio of “tree-in-bud” was 42.91 (95% CI: 5.62–327.42). Using an optimal threshold of 51 spots, quantitative IGRA yielded 64% sensitivity (95% CI: 44–84%) and 61% specificity (95% CI: 50–73%) for the diagnosis of active tuberculosis.
In a low incidence setting, chest CT, especially when “tree-in-bud” pattern is present, is superior to quantitative IGRA testing to identify patients with active tuberculosis among those with positive IGRA testing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite the wide use of the 6 min walk distance (6MWD), no study has ever assessed its validity as a surrogate marker for haemodynamics and predictor of outcome in isolated pulmonary arterial ...hypertension associated with systemic sclerosis (SSc-PAH). We designed this work to address this issue.
Treatment-naïve patients with SSc-PAH were prospectively included from two sources: the French PAH Network (a prospective epidemiological cohort) (n=83) and randomised clinical trials submitted for drug approval (Food and Drug Administration) (n=332). Correlations between absolute values of the 6MWD and haemodynamics at baseline, as well as between variations of 6MWD and haemodynamics during follow-up, were studied in both populations.
In the French cohort, baseline cardiac output (CO) (R(2)=0.19, p=0.001) and New York Heart Association class (R(2)=0.10, p<0.001) were significantly and independently correlated with baseline 6MWD in multivariate analysis. A significant, independent, but weaker, correlation with CO was also found in the Food and Drug Administration sample (R(2)=0.04, p<0.001). During follow-up, there was no association between the changes in 6MWD and haemodynamic parameters in patients under PAH-specific treatments.
In SSc-PAH, CO independently correlates with 6MWD at baseline, but accounts for a small amount of the variance of 6MWD in both study samples. This suggests that other non-haemodynamic factors could have an impact on the walk distance. Moreover, variations of 6MWD do not reflect changes in haemodynamics among treated patients. Our results suggest that 6MWD is not an accurate surrogate marker for haemodynamic severity, nor an appropriate outcome measure to assess changes in haemodynamics during follow-up in treated SSc-PAH.
The role of health-related quality of life (HRQoL) and psychological variables in pulmonary arterial hypertension (PAH) progression remains poorly quantified. We aimed to investigate the relationship ...between disease progression in PAH patients and HRQoL and psychological characteristics.
A 3-year longitudinal cohort was initiated. Patients with stable PAH (groups I-IV ineligible for angioplasty/endarterectomy) were included (n=55). Standard clinical variables, including invasive haemodynamic parameters, were prospectively recorded. A battery of questionnaires was used to characterise the psychological status of patients upon study initiation, and HRQoL was quantified using the SF-36 Questionnaire every 3 months for 24 months, and then again at 36 months. Guideline-defined disease progression and progression-free survival were recorded for 36 months.
Psychological distress was highly prevalent at baseline. The Physical Component Summary (PCS) and the Mental Component Summary (MCS) of the HRQoL were poor (PCS=37.13±8.18; MCS=42.42±10.88) but stable over 3 years of follow-up. Among PCS subscales, Physical Functioning (PF) (p=0.012) was identified as being independently associated with disease progression (Cox survival model), along with mean pulmonary arterial pressure (p=0.003) and cardiac output (p=0.005). Depression was the unique independent psychological characteristic associated with PF (p=0.0001).
PAH patients have poor HRQoL. In addition to already known criteria related to disease severity, the HRQoL PF subscale is independently associated with disease progression in PAH. This may be explained by depression.
The landscape of asthma has considerably changed after 40 years of inhaled corticosteroid development and nearly 20 years since the first monoclonal antibodies (mAbs) were approved. New members of ...pharmacological families and more effective drug-delivery devices have been designed but the proportion of uncontrolled patients, unfortunately, remains stable. The most promising treatments now rely on targeted therapies that encourage the improvement of the characterisation of our patients. These clinical (phenotype) or new biological (endotype) tools lead to palpable personalised medicine. This review examines not only the future of mAbs and other new ways of treating asthma but also describes futuristic views based on the paradigm shifts that are ready to occur.
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