Primary cardiac lymphoma: diagnosis, treatment and outcome in a modern series.

Primary cardiac lymphoma (PCL) represents a rare subset of extranodal lymphomas for which the primary lesion arises from the heart and/or the pericardium. Fundamental characteristics of PCL remain uncertain, regarding optimal diagnosis strategy, pathological features, treatments, as well as prognostic factors. This is a single-institution retrospective study of patients with histologically proven lymphoma, presenting with exclusive or predominant myocardial invasion at time of diagnosis. Thirteen patients were included, all of whom had symptoms related to cardiac tumour location with chronic chest pain in six (46%), dyspnea in seven (54%) and arythmia in three (23%). Sub-acute and acute congestive heart failure were noticed in respectively nine (70%) and one (9%). PCL was identified at transthoracic echocardiography and computed tomography scan in 80 and 100% of patients, respectively. Most frequent location was the right atrium in 10 (77%) patients. Pericardial effusion was identified in 10 (77%). Pathological diagnosis-diffuse large B-cell lymphoma in 12 cases and Burkitt in 1 case-was made on cardiac surgical biopsies in 9 cases and by intravascular procedure in 2 cases. All patients received first-line chemotherapy, with a complete response rate of 62%. Recurrences occurred in 55% of patients, mostly at extracardiac extranodal sites. Our data confirm that PCL harbours specific clinical and anatomical features. The aggressiveness of PCL mainly results from the possible onset of acute cardiac events. Further molecular characterization may help to further individualize PCL among diffuse and intrathoracic lymphomas. Copyright © 2016 John Wiley & Sons, Ltd.

Connective tissue diseases, multimorbidity and the ageing lung.

Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients.

Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail.In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease.The study population included 157 patients (mean±sd age 49.4±14.1 years), with a mean±sd blood eosinophil count of 7.4±6.4×109 L-1 at diagnosis. There was a mean±sd of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3-6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively.In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity.

Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis.

Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis.We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival.237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046).TERT/TERC DAV were associated with specific clinical and biological features and reduced transplant-free survival.

A prospective study of the 6†min walk test as a surrogate marker for haemodynamics in two independent cohorts of treatment-naïve systemic sclerosis-associated pulmonary arterial hypertension.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Many Faces of Bronchiolitis and Organizing Pneumonia.

As the bronchioles have a strategic position between the airways and the alveolar structures, they are at a site where disorders of many origins may develop, including infections, inflammatory and/or fibrosing processes of immune, occupational, environmental, tumoral, and iatrogenic origin, which may result in predominant bronchiolitis and/or organizing pneumonia. This etiologic variety results in many distinct entities and syndromes, common or rare, with new or renewed faces such as bronchiolocentric interstitial pneumonia or organizing pneumonia primed by radiation to the breast.

Severe Prolonged Cough as Presenting Manifestation of FIP1L1-PDGFRA+ Chronic Eosinophilic Leukaemia: A Widely Ignored Association.

Chronic eosinophilic leukaemia associated with the FIP1L1-PDGFRA fusion gene (F/P+ CEL) is a rare cause of marked persistent hypereosinophilia, arising almost exclusively in male patients. Clinical presentations are heterogeneous with a higher incidence of eosinophil-mediated cardiomyopathy than in other hypereosinophilic syndrome variants. Features of chronic myeloproliferative disease are often present, including splenomegaly and elevated serum vitamin B12 levels. The diagnosis is made by fluorescence in situ hybridization (FISH) showing the deletion of the CHIC2 locus and/or RT-PCR showing the FIP1L1-PDGFRA fusion transcript. Treatment with imatinib mesylate, a tyrosine kinase inhibitor, results in rapid and complete resolution of hypereosinophilia and associated symptoms, except for those related to sub-endocardial fibrosis that may be irreversible. We report the case of a male patient in whom isolated intractable cough remained the only clinical manifestation of F/P+ CEL for 4 years. Furthermore, eosinophil autofluorescence, an as yet unreported artefact in this setting, precluded the detection of the CHIC2 deletion and further delayed diagnosis, underlining that both FISH and RT-PCR should be performed when this disease is suspected.

Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension.

BACKGROUND: Patients treated for pulmonary arterial hypertension (PAH) frequently receive vitamin K antagonists (VKAs) for PAH or validated indications (such as atrial fibrillation or venous thromboembolism). In these latter indications, VKAs are challenged by direct oral anticoagulants (DOAs). Decreased dosage of DOAs has been proposed in patients at risk of bioaccumulation. OBJECTIVES: We aimed to evaluate the frequency of bioaccumulation risks in patients treated with PAH-targeted therapy, particularly regarding the presence of validated indications. METHODS: We conducted a retrospective study in three different PAH referral centers. All patients receiving PAH-targeted therapy were classified according to demographics, prescription and indications of VKAs, and the presence of major bioaccumulation risk factors (renal failure, low body weight, strong P-glycoprotein or cytochrome P3A4 inhibitors). RESULTS: Two hundred and thirty-nine of the 366 patients included received VKAs, 94 for validated indications. At least one major risk factor was found in 231 (63.1%) of the whole study population, and in 54 (57.4%) of the patients anticoagulated for a validated indication. No specific patient phenotype could be individualized. CONCLUSIONS: About 1 in 2 patients treated with PAH therapy has at least one of the three major risk factors for DOA bioaccumulation. DOAs in the PH setting could be associated with bioaccumulation and should be individualized, mainly in patients with confirmed indication.

Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension.

Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6 months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6 months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension.

Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis.

Pulmonary fibrosis is a fatal disease with progressive loss of respiratory function. Defective telomere maintenance leading to telomere shortening is a cause of pulmonary fibrosis, as mutations in the telomerase component genes TERT (reverse transcriptase) and TERC (RNA component) are found in 15% of familial pulmonary fibrosis (FPF) cases. However, so far, about 85% of FPF remain genetically uncharacterised.Here, in order to identify new genetic causes of FPF, we performed whole-exome sequencing, with a candidate-gene approach, of 47 affected subjects from 35 families with FPF without TERT and TERC mutations.We identified heterozygous mutations in regulator of telomere elongation helicase 1 (RTEL1) in four families. RTEL1 is a DNA helicase with roles in DNA replication, genome stability, DNA repair and telomere maintenance. The heterozygous RTEL1 mutations segregated as an autosomal dominant trait in FPF, and were predicted by structural analyses to severely affect the function and/or stability of RTEL1. In agreement with this, RTEL1-mutated patients exhibited short telomeres in comparison with age-matched controls.Our results provide evidence that heterozygous RTEL1 mutations are responsible for FPF and, thereby, extend the clinical spectrum of RTEL1 deficiency. Thus, RTEL1 enlarges the number of telomere-associated genes implicated in FPF.

Inflammatory bowel diseases in anti-neutrophil cytoplasmic antibody-associated vasculitides: 11 retrospective cases from the French Vasculitis Study Group.

OBJECTIVE: Coexistence of ANCA-associated vasculitis (AAV) and IBD is a rare condition that is rarely described in the literature. The aim of the study was to describe the main characteristics of patients presenting with both IBD and AAV. METHODS: A retrospective study of AAV patients in the French Vasculitis Study Group cohort who also had a diagnosis of IBD was conducted. We reviewed the medical records and outcomes of these patients. RESULTS: We identified 11 patients with AAV and IBD. Four patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss) also had ulcerative colitis and seven patients with granulomatosis with polyangiitis (GPA) had Crohn's disease. No Crohn's disease was observed in eosinophilic GPA and no ulcerative colitis in GPA. IBD started before AAV manifestations in six cases, simultaneously in two cases and after AAV manifestations in three cases. CONCLUSION: Coexistence of IBD and AAV is a rare condition. The therapeutic management of these patients includes corticosteroids in all cases and immunosuppressive drugs in some patients. Coexistence of IBD and AAV might be explained by common underlying inflammatory responses and cytokine profiles polarized towards either Th1 or Th2. Finally, in the presence of digestive manifestations in the context of AAV, the hypothesis of IBD should be assessed.

Usual interstitial pneumonia end-stage features from explants with radiologic and pathological correlations.

Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia, with typical high-resolution computed tomography (HRCT) features and histologic pattern of usual interstitial pneumonia (UIP); its main differential diagnosis is fibrotic nonspecific interstitial pneumonia (F-NSIP). Usual interstitial pneumonia was mainly described from lung biopsies, and little is known on explants. Twenty-two UIP/IPF explants were analyzed histologically and compared with previous open lung biopsies (OLBs; n = 11) and HRCT (n = 19), when available. Temporospatial heterogeneity and subpleural and paraseptal fibrosis were similarly found in UIP/IPF explants and OLB (91%-95%). Fibroblastic foci were found in 82% of OLBs and 100% of explants, with a higher mean score in explants (P = .023). Honeycombing was present in 64% of OLBs and 95% of explants, with a higher mean score in explants (P = .005). Almost 60% of UIP/IPF explants showed NSIP areas and 41% peribronchiolar fibrosis; inflammation, bronchiolar metaplasia, and vascular changes were more frequent in UIP/IPF explants; and Desquamative Interstitial Pneumonia (DIP)-like areas were not common (18%-27%). Numerous large airspace enlargements with fibrosis were frequent in UIP/IPF explants (59%). On HRCT, honeycombing was observed in 95% of the cases and ground-glass opacities in 53%, correlating with NSIP areas or acute exacerbation at histology. Six patients had combined IPF and emphysema. Lesions were more severe in UIP/IPF explants, reflecting the worsening of the disease. Usual interstitial pneumonia/IPF explants more frequently presented with confounding lesions such as NSIP areas, peribronchiolar fibrosis, and airspace enlargements with fibrosis sometimes associated with emphysema.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort.

OBJECTIVE: Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long-term outcomes. METHODS: A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis. RESULTS: We identified 383 patients diagnosed between 1957 and June 2009 (128 [33.4%] before 1997 or earlier) and followed up for a mean±SD of 66.8±62.5 months. At diagnosis, their mean±SD age was 50.3±15.7 years, and 91.1% had asthma (duration 9.3±10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA-positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA-negative patients. Vasculitis relapses occurred in 35.2% of the ANCA-positive versus 22.5% of the ANCA-negative patients (P=0.01), and 5.6% versus 12.5%, respectively, died (P<0.05). The 5-year relapse-free survival rate was 58.1% (95% confidence interval [95% CI] 45.6-68.6) for ANCA-positive and 67.8% (95% CI 59.8-74.5) for ANCA-negative patients (P=0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse. CONCLUSION: The characteristics and long-term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.

[Not Available]. / Fibrose pulmonaire idiopathique: progrès étiologiques, diagnostiques, et thérapeutiques.

Idiopathic pulmonary fibrosis usually develops after 60 years of age, especially in men, leading to progressive exercise dyspnea. Median survival is about 3 years after diagnosis. This disease emerged in the middle of the last century and is linked to smoking. Mutations of genes encoding surfactant proteins and the telomerase complex may occasionally be present. International diagnostic criteria based on histopathology and computed tomography (CT) define the diagnosis as definite, probable or possible. Recent treatments (pirfenidone and nintedanib) have proven beneficial. Therapeutic advances warrant earlier diagnosis, based on Velcro crackles on pulmonary auscultation or interstitial opacities on CT screening for lung cancer.

Neglected evidence in idiopathic pulmonary fibrosis: from history to earlier diagnosis.

This perspective highlights some evidence that has hitherto been neglected, especially because it may not have been sufficiently explicated in the clinical respiratory medicine literature. Idiopathic pulmonary fibrosis (IPF) has appeared only in the second half of the 20th century and, like lung cancer and chronic obstructive pulmonary disease, may be a direct consequence of the cigarette smoking epidemic. It is a disease of lung ageing, with most affected patients being >70 years of age. The relationship between lung ageing and pulmonary fibrosis is further illustrated in the bleomycin mouse model, in which older males develop more fibrosis than young female mice. Earlier diagnosis of IPF is a prerequisite for significant progress to be made in the long-term outcome and prognosis. We consider that only two different yet complementary and realistic approaches could lead to earlier diagnosis of IPF and possibly to allowing more efficient disease management: 1) investigating any patients with early Velcro crackles at lung auscultation through proactive education of, and commitment from, primary care physicians; and 2) using current large-scale lung cancer screening strategies with low-dose high-resolution computed tomography in smokers for the detection of subclinical interstitial lung disease and especially early IPF.

Hypereosinophilic obliterative bronchiolitis: a distinct, unrecognised syndrome.

Biopsy-proven cases of eosinophilic bronchiolitis have only been reported in isolation, and all come from Japan. We present six patients with hypereosinophilic obliterative bronchiolitis (HOB), defined by the following criteria: 1) blood eosinophil cell count >1 G·L(-1) and/or bronchoalveolar lavage eosinophil count >25%; 2) persistent airflow obstruction despite high-dose inhaled bronchodilators and corticosteroids; and 3) eosinophilic bronchiolitis at lung biopsy (n=1) and/or direct signs of bronchiolitis (centrilobular nodules and branching opacities) on computed tomography (n=6). Chronic dyspnoea and cough which was often severe, without the characteristic features of asthma, were the main clinical manifestations. Atopy and asthma were present in the history of three and two patients, respectively. One patient met biological criteria of the lymphoid variant of idiopathic hypereosinophilic syndrome. Mean blood eosinophil cell count was 2.7 G·L(-1) and mean eosinophil differential percentage at bronchoalveolar lavage was 63%. Mean initial forced expiratory volume in 1 s/forced vital capacity ratio was 50%, normalising with oral corticosteroid therapy in all patients. HOB manifestations recurred when oral prednisone was decreased to 10-20 mg·day(-1), but higher doses controlled the disease. HOB is a characteristic entity deserving to be individualised among the eosinophilic respiratory disorders. Thorough analysis is needed to determine whether unrecognised and/or smouldering HOB may further be a cause of irreversible airflow obstruction in chronic eosinophilic respiratory diseases.

Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis.

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean ± sd 1.6 ± 1.1 versus 5.3 ± 4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.

Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era.

OBJECTIVE: To assess the survival and prognostic factors in patients with newly diagnosed incident systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) in the modern management era. METHODS: Prospectively enrolled SSc patients in the French PAH Network between January 2006 and November 2009, with newly diagnosed PAH and no interstitial lung disease, were analysed (85 patients, mean age 64.9±12.2 years). Median follow-up after PAH diagnosis was 2.32 years. RESULTS: A majority of patients were in NYHA functional class III-IV (79%). Overall survival was 90% (95% CI 81% to 95%), 78% (95% CI 67% to 86%) and 56% (95% CI 42% to 68%) at 1, 2 and 3 years from PAH diagnosis, respectively. Age (HR: 1.05, 95% CI 1.01 to 1.09, p=0.012) and cardiac index (HR: 0.49, 95% CI 0.27 to 0.89, p=0.019) were significant predictors in the univariate analysis. We also observed strong trends for gender, SSc subtypes, New York Heart Association functional class, pulmonary vascular resistance and capacitance to be significant predictors in the univariate analysis. Conversely, six-min walk distance, mean pulmonary arterial and right atrial pressures were not significant predictors. In the multivariate model, gender was the only independent factor associated with survival (HR: 4.76, 95% CI 1.35 to 16.66, p=0.015 for male gender). CONCLUSIONS: Incident SSc-associated PAH remains a devastating disease even in the modern management era. Age, male gender and cardiac index were the main prognosis factors in this cohort of patients. Early detection of less severe patients should be a priority.

Pulmonary hypertension in lymphangioleiomyomatosis: characteristics in 20 patients.

This retrospective, multicentre study evaluated patients with lymphangioleiomyomatosis (LAM) and pre-capillary pulmonary hypertension (PH) by right heart catheterisation. It was conducted in 20 females with a mean ± SD age of 49 ± 12 yrs and a mean ± SD time interval between LAM and PH diagnoses of 9.2 ± 9.8 yrs. All, except for one patient, were receiving supplemental oxygen. 6-min walking distance was mean ± SD 340 ± 84 m. Haemodynamic characteristics were: mean pulmonary artery pressure (PAP) 32 ± 6 mmHg, cardiac index 3.5 ± 1.1 L · min(-1) · m(-2) and pulmonary vascular resistance (PVR) 376 ± 184 dyn · s · cm(-5). Mean PAP was >35 mmHg in only 20% of cases. The forced expiratory volume in 1 s was 42 ± 25%, carbon monoxide transfer factor was 29 ± 13%, and arterial oxygen tension (P(a,O(2))) was 7.4 ± 1.3 kPa in room air. Mean PAP and PVR did not correlate with P(a,O(2)). In six patients who received oral pulmonary arterial hypertension (PAH) therapy, the PAP decreased from 33 ± 9 mmHg to 24 ± 10 mmHg and the PVR decreased from 481 ± 188 dyn · s · cm(-5) to 280 ± 79 dyn · s · cm(-5). The overall probability of survival was 94% at 2 yrs. Pre-capillary PH of mild haemodynamic severity may occur in patients with LAM, even with mild pulmonary function impairment. PAH therapy might improve the haemodynamics in PH associated with LAM.