Development and prospective validation of a model for predicting weaning in chronic ventilator dependent patients

Background

HTLV-I infection has been linked to lung pathology and HTLV-II has been associated with an increased incidence of pneumonia and acute bronchitis. However it is unknown whether HTLV-I or -II infection alters pulmonary function.

Methods

We performed pulmonary function testing on HTLV-I, HTLV-II and HTLV seronegative subjects from the HTLV outcomes study (HOST), including vital capacity (VC), forced expiratory volume in one second (FEV₁), and diffusing lung capacity for carbon monoxide (DLCO) corrected for hemoglobin and lung volume. Multivariable analysis adjusted for differences in age, gender, race/ethnicity, height and smoking history.

Results

Mean (standard deviation) pulmonary function values among the 257 subjects were as follows: FVC = 3.74 (0.89) L, FEV₁ = 2.93 (0.67) L, DLCO_corr = 23.82 (5.89) ml/min/mmHg, alveolar ventilation (VA) = 5.25 (1.20) L and DLCO_corr/VA = 4.54 (0.87) ml/min/mmHg/L. There were no differences in FVC, FEV1 and DLCO_corr/VA by HTLV status. For DLCO_corr, HTLV-I and HTLV-II subjects had slightly lower values than seronegatives, but neither difference was statistically significant after adjustment for confounding.

Conclusions

There was no difference in measured pulmonary function and diffusing capacity in generally healthy HTLV-I and HTLV-II subjects compared to seronegatives. These results suggest that previously described HTLV-associated abnormalities in bronchoalveolar cells and fluid may not affect pulmonary function.     

Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study

Introduction

Pulmonary involvement represents a major cause of death of systemic sclerosis (SSc) patients. Recent data suggest that tyrosine kinase inhibitors, such as imatinib, may be a therapeutic option for SSc patients. However, preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects. The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy.

Methods

Thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. A “good response” was defined as an increase of forced vital capacity (FVC) by more of 15% and/or increase of diffusing capacity of carbon monoxide (DL_CO) >15% and PaO₂ > 90% of initial value and high-resolution computed tomography (HRCT)-scan pattern unchanged or improved.

Results

Twenty-six patients completed the study. Three patients died and one patient was lost to follow-up. Four patients (15.32%) had a good response, 7 worsened and 15 had a stabilized lung disease. Overall, 19 (73.07%) patients had an improved or stabilized lung disease. After a 6-month follow-up, 12 (54.5%) of the 22 patients showed an improved or stabilized lung disease.

Conclusions

Lung function was stabilized in a large proportion of patients unresponsive to cyclophosphamide therapy and a beneficial outcome emerged from the analysis of HRCT lung scans. There was no significant improvement of skin involvement, and the low dose was well tolerated. These data provide useful suggestions to design future randomized clinical trials for SSc therapeutics.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00573326","term_id":"NCT00573326"}}NCT00573326. Registered 13 December 2007.     

Evaluation of Current Knowledge, Awareness and Practice of Spirometry among Hospital -based Nigerian Doctors

Background

The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.

Methods

Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography.

Results

Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and D_LCO were independent predictors of systolic pulmonary artery pressure.

Conclusion

Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.     

Factors affecting treatment outcome in patients with idiopathic nonspecific interstitial pneumonia: a nationwide cohort study

Background

The effects of corticosteroid-based therapy in patients with idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting treatment outcome, are not fully understood. We aimed to investigate the long-term treatment response and factors affecting the treatment outcome in iNSIP patients from a multi-center study in Korea.

Methods

The Korean interstitial lung disease (ILD) Study Group surveyed ILD patients from 2003 to 2007. Patients were divided into two groups to compare the treatment response: response group (forced vital capacity (FVC) improves ≥10% after 1 year) and non-response group (FVC <10%). Factors affecting treatment response were evaluated by multivariate logistic regression analysis.

Results

A total of 261 patients with iNSIP were enrolled, and 95 patients were followed-up for more than 1 year. Corticosteroid treatment was performed in 86 patients. The treatment group showed a significant improvement in lung function after 1-year: FVC, 10.0%; forced expiratory volume (FEV₁), 9.8%; diffusing capacity of the lung for carbon monoxide (DLco), 8.4% (p?<?0.001). Sero-negative anti-nuclear antibody (ANA) was significantly related with lung function improvement. Sero-positivity ANA was significantly lower in the response group (p?=?0.013), compared to that in the non-response group. A shorter duration of respiratory symptoms at diagnosis was significantly associated with a good response to treatment (p?=?0.018).

Conclusion

Treatment with corticosteroids and/or immunosuppressants improved lung function in iNSIP patients, which was more pronounced in sero-negative ANA and shorter symptom duration patients. These findings suggest that early treatment should be considered in iNSIP patients, even in an early disease stage.

     

Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis

Introduction

Autoantibodies to Ro52 recently identified as TRIM21 are among the most common autoantibodies in systemic autoimmune rheumatic diseases, but their clinical association remains poorly understood. We undertook this study to determine the clinical and serologic associations of anti-Ro52/TRIM21 antibodies in patients with systemic sclerosis (SSc).

Methods

Detailed clinical data and sera from 963 patients with SSc enrolled in a multicenter cohort study were collected and entered into a central database. Antibodies to Ro52/TRIM21 and other autoantibodies were detected with an addressable laser-bead immunoassay and different enzyme-linked immunosorbent assay (ELISA) systems. Associations between anti-Ro52/TRIM21 antibodies and clinical and other serologic manifestations of SSc were investigated.

Results

Anti-Ro52/TRIM21 antibodies were present in 20% of SSc patients and overlapped with other main SSc-related antibodies, including anti-centromere (by immunofluorescence and centromere protein (CENP)-A and CENP-B ELISA), anti-topoisomerase I, anti-RNA polymerase III, and anti-Pm/Scl antibodies. Anti-Ro52/TRIM21 antibodies were strongly associated with interstitial lung disease (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.11 to 2.12; P = 0.0091) and overlap syndrome (OR, 2.06; 95% CI, 1.01 to 4.19; P = 0.0059).

Conclusions

Anti-Ro52/TRIM21 antibodies were the second most common autoantibodies in this SSc cohort. In SSc, anti-Ro52/TRIM21 antibodies may be a marker of interstitial lung disease and overlap syndrome.     

Quantitative videocapillaroscopy correlates with functional respiratory parameters: a clue for vasculopathy as a pathogenic mechanism for lung injury in systemic sclerosis

Background

To determine whether lung involvement is related to microvascular perturbations, nailfold videocapillaroscopy (NVC) was performed in patients with systemic sclerosis (SSc).

Methods

A cross-sectional study was consecutively accomplished in 152 SSc patients. NVC, a pulmonary function test and echocardiography were undergone within a 3-month period. Finally, 134 patients with at least eight NVC (200× magnification) images were selected for quantitative and qualitative examinations.

Results

Patients with interstitial lung disease presented lower median capillary density (4.86/mm vs 5.88/mm, p =?0.005) and higher median of neoangiogenesis (0.56/mm vs 0.31/mm, p =?0.005). A higher quantity of neoangiogenesis capillaries was found in patients with pulmonary arterial hypertension (0.70/mm vs 0.33/mm, p =?0.008). Multivariate linear regression analysis established a correlation between neoangiogenesis and decreased forced vital capacity (FVC) (p <?0.001): for each capillary with neoangiogenesis visualized on average per 1?mm, FVC was 7.3% reduced. In qualitative NVC, a late pattern as defined by Cutolo was also associated with lower FVC (p =?0.018). The number of giant capillaries was associated with reduced diffusion capacity of the lung for carbon monoxide (DLCO) (p =?0.016); for each giant capillary per 1?mm, DLCO was 11.8% diminished.

Conclusions

A good correlation was observed between distinctive quantitative and qualitative NVC features with lung functional parameters such as FVC and DLCO. It is suggested that vasculopathy could play a role in SSc lung involvement.

     

MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression.

Methods and Findings

We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins—MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A—that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%–100%) and specificity of 98.1% (95% CI 89.9%–100%). Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%–100%) and specificity of 87.2% (95% CI 72.6%–95.7%). We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD), as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC%) and percent predicted carbon monoxide diffusing capacity (DL_CO%).

Conclusions

Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung microenvironment and distinguish IPF from other chronic lung diseases. Additionally, increased MMP7 concentration may be indicative of asymptomatic ILD and reflect disease progression.     

Computer-Aided Tomographic Analysis of Interstitial Lung Disease (ILD) in Patients with Systemic Sclerosis (SSc). Correlation with Pulmonary Physiologic Tests and Patient-Centred Measures of Perceived Dyspnea and Functional Disability

Objectives

This study was designed (a) to evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CaM) system in patients with systemic sclerosis (SSc),—related interstitial lung disease (SSc-ILD), (b) to investigate the relationship between physiologic parameters (forced vital capacity [FVC] and single-breath diffusing capacity for carbon monoxide [DLCO]), patient-centred measures of dyspnea and functional disability and CaM and visual reader-based (CoVR) methods, and (c) to identify potential surrogate measures from quantitative and visual HRCT measurement.

Methods

126 patients with SSc underwent chest radiography, HRCT and PFTs. The following patient-centred measures were obtained: modified Borg Dyspnea Index (Borg score), VAS for breathing, and Health Assessment Questionnaire-Disability Index (HAQ-DI). HRCT abnormalities were scored according to the conventional visual reader-based score (CoVR) and by a CaM. The relationships among the HRCT scores, physiologic parameters (FVC and DLCO, % predicted) results and patient-centred measures, were calculated using linear regression analysis and Pearson’s correlation. Multivariate regression models were performed to identify the predictor variables on severity of pulmonary fibrosis.

Results

Subjects with limited cutaneous SSc had lower HAQ-DI scores than subjects with diffuse cutaneous SSc (p <0.001). CaM and CoVR scores were similar in the 2 groups. In univariate analysis, a strong correlation between CaM and CoVR was observed (p <0.0001). In multivariate analysis the CaM and CoVR scores were predicted by DLco, FVC, Borg score and HAQ-DI. Age, sex, disease duration, anti-topoisomerase antibodies and mRSS were not significantly associated with severity of pulmonary fibrosis on CaM- and CoVR methods.

Conclusions

Although a close correlation between CaM score results and CoVR total score was found, CaM analysis showed a more significant correlation with DLco (more so than the FVC), patient-centred measures of perceived dyspnea and functional disability. Computer-aided tomographic analysis is computationally efficient, and in combination with physiologic and patient-centred measures, it could allow a means for accurately assessing and monitoring the disease progression or response to therapy.     

Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study

Background

Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.

Methods

We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.

Results

Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.

Conclusions

Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.

     

Glucocorticoid receptor gene polymorphisms associated with progression of lung disease in young patients with cystic fibrosis

Background

The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to variations in the inflammatory response.

Methods

We evaluated the association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and BclI, and disease progression in a cohort of 255 young patients with CF. Genotypes were tested for association with changes in lung function tests, infection with Pseudomonas aeruginosa and nutritional status by multivariable analysis.

Results

A significant non-corrected for multiple tests association was found between BclI genotypes and decline in lung function measured as the forced expiratory volume in one second (FEV₁) and the forced vital capacity (FVC). Deterioration in FEV₁ and FVC was more pronounced in patients with the BclI GG genotype compared to the group of patients with BclI CG and CC genotypes (p = 0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02 respectively for F508del homozygous patients).

Conclusion

The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function.     

No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products - a pilot study

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which rapidly leads to chronic respiratory failure requiring mechanical ventilation. Currently, forced vital capacity (FVC) < 50% is considered as physiologic marker for admitting patients to Noninvasive Positive Pressure Ventilation (NPPV) intervention, although it has been recently shown the median survival of patients with baseline FVC < 75% much shorter than median survival of patients with baseline FVC > 75%, independently by any treatment.

Aim

To assess the role of NPPV in improving outcome of ALS, a retrospective analysis was performed to investigate 1 year survival of ALS patients with FVC < 75% and nocturnal respiratory insufficiency, treated with NPPV, compared to a well-matched population of ALS patients, who refused or was intolerant to NPPV.

Methods

We investigated seventy-two consecutive ALS patients who underwent pulmonary function test. Forty-four presented a FVC > 75% and served as control group. Twenty-eight patients presented a FVC < 75% and showed, at polysomnography analysis, nocturnal respiratory insufficiency, requiring NPPV; sixteen were treated with NPPV, while twelve refused or were intolerant.

Results

Increased survival rate at 1 year in patients with FVC < 75% treated with NPPV, as compared to those who refused or could not tolerate NPPV (p = 0.02), was observed. The median rate of decline in FVC% was slower in NPPV patients than in patients who did not use NPPV (95% CI: 0.72 to 1.85; p < 0.0001).

Conclusion

This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS.     

Diagnostic value of anti-topoisomerase I antibodies in a large monocentric cohort

Introduction

In the present study, the detection of anti-topoisomerase I (anti-topo I) autoantibodies was evaluated for diagnosis and risk assessment of systemic sclerosis (SSc) patients in a well characterized large monocentric cohort.

Methods

Sera from patients with SSc (diffuse n = 96, limited n = 113), from patients with overlap syndromes (n = 51), from patients with other diseases associated with SSc (n = 20), as well as from disease controls (n = 487) were analysed for the presence of anti-topo I antibodies by line immunoblot assay and ELISA. Assessment of organ manifestations was performed as proposed by the European Scleroderma Trial and Research network.

Results

The applied test systems for the detection of anti-topo I antibodies revealed a diagnostic sensitivity for SSc of approximately 24% and a diagnostic specificity of at least 99.6%. The sensitivity to identify patients with diffuse SSc amounted to 60%. Patients with anti-topo I antibodies showed a higher burden of skin and lung fibrosis, contractures, electrocardiogram changes, as well as digital ulcers and had more active disease than antibody-negative patients. Signal strengths correlated only weakly with disease activity, with modified Rodnan skin score, with predicted forced vital capacity, and with predicted diffusion capacity levels (P = 0.01, ρ = 0.234, ρ = 0.413, ρ = -0.215, ρ = -0.219). High signal intensities were associated with an increased mortality in diffuse SSc patients (P = 0.003).

Conclusions

Diagnosis and risk assessment of SSc patients can be supported by the detection of anti-topo I antibodies. Signal intensities as obtained by line immunoblot assay or ELISA can be used as a surrogate marker for fibrosis, active disease and worse prognosis.     

Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients

Background

The clinical manifestations of severe asthma are heterogeneous. Some individuals with severe asthma develop irreversible fixed airway obstruction, which is associated with poor outcomes. We therefore investigated the factors associated with fixed airway obstruction in Korean patients with severe asthma.

Methods

Severe asthma patients from a Korean adult asthma cohort were divided into two groups according to the results of serial pulmonary function tests. One group had fixed airway obstruction (FAO) [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7, n = 119] and the other had reversible airway obstruction (RAO) [FEV1/FVC ratio ≥ 0.7, n = 116]. Clinical and demographic parameters were compared between the two groups.

Results

Multivariate analysis showed that longer duration of disease, greater amount of cigarette smoking and absence of rhinosinusitis were significantly related to the development of FAO in severe asthmatics. Other parameters, including atopic status, pattern of airway inflammatory cells in induced sputum, and frequency of asthma exacerbations did not differ between the FAO and RAO groups.

Conclusion

Severe asthma patients with longer disease duration and the absence of rhinosinusitis are more likely to develop FAO. This study also demonstrates the importance of quitting smoking in order to prevent irreversible airway obstruction. Further investigation is required to determine the mechanism by which these factors can modify the disease course in Korean patients with severe asthma.     

Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas

Background

To gain biological insights into lung metastases from hepatocellular carcinoma (HCC), we compared the whole-genome sequencing profiles of primary HCC and paired lung metastases.

Methods

We used whole-genome sequencing at 33X-43X coverage to profile somatic mutations in primary HCC (HBV+) and metachronous lung metastases (> 2 years interval).

Results

In total, 5,027-13,961 and 5,275-12,624 somatic single-nucleotide variants (SNVs) were detected in primary HCC and lung metastases, respectively. Generally, 38.88-78.49% of SNVs detected in metastases were present in primary tumors. We identified 65–221 structural variations (SVs) in primary tumors and 60–232 SVs in metastases. Comparison of these SVs shows very similar and largely overlapped mutated segments between primary and metastatic tumors. Copy number alterations between primary and metastatic pairs were also found to be closely related. Together, these preservations in genomic profiles from liver primary tumors to metachronous lung metastases indicate that the genomic features during tumorigenesis may be retained during metastasis.

Conclusions

We found very similar genomic alterations between primary and metastatic tumors, with a few mutations found specifically in lung metastases, which may explain the clinical observation that both primary and metastatic tumors are usually sensitive or resistant to the same systemic treatments.     

Design of the Endobronchial Valve for Emphysema Palliation Trial (VENT): a non-surgical method of lung volume reduction

Background

Lung volume reduction surgery is effective at improving lung function, quality of life, and mortality in carefully selected individuals with advanced emphysema. Recently, less invasive bronchoscopic approaches have been designed to utilize these principles while avoiding the associated perioperative risks. The Endobronchial Valve for Emphysema PalliatioN Trial (VENT) posits that occlusion of a single pulmonary lobe through bronchoscopically placed Zephyr^® endobronchial valves will effect significant improvements in lung function and exercise tolerance with an acceptable risk profile in advanced emphysema.

Methods

The trial design posted on Clinical trials.gov, on August 10, 2005 proposed an enrollment of 270 subjects. Inclusion criteria included: diagnosis of emphysema with forced expiratory volume in one second (FEV₁) < 45% of predicted, hyperinflation (total lung capacity measured by body plethysmography > 100%; residual volume > 150% predicted), and heterogeneous emphysema defined using a quantitative chest computed tomography algorithm. Following standardized pulmonary rehabilitation, patients were randomized 2:1 to receive unilateral lobar placement of endobronchial valves plus optimal medical management or optimal medical management alone. The co-primary endpoint was the mean percent change in FEV₁ and six minute walk distance at 180 days. Secondary end-points included mean percent change in St. George's Respiratory Questionnaire score and the mean absolute changes in the maximal work load measured by cycle ergometry, dyspnea (mMRC) score, and total oxygen use per day. Per patient response rates in clinically significant improvement/maintenance of FEV₁ and six minute walk distance and technical success rates of valve placement were recorded. Apriori response predictors based on quantitative CT and lung physiology were defined.

Conclusion

If endobronchial valves improve FEV₁ and health status with an acceptable safety profile in advanced emphysema, they would offer a novel intervention for this progressive and debilitating disease.

Trial Registration

ClinicalTrials.gov: NCT00129584     

Borderline pulmonary arterial pressure in systemic sclerosis patients: a post-hoc analysis of the DETECT study

Introduction

Patients with mean pulmonary artery pressures (mPAP) of 21 to 24 mm Hg have a so-called borderline elevation of mPAP (BoPAP)—a condition thought to represent early-stage pulmonary arterial vasculopathy. Based on the DETECT study, this post-hoc analysis examined patient characteristics of systemic sclerosis (SSc) patients with normal mPAP, BoPAP and elevated mPAP, fulfilling pulmonary arterial hypertension (PAH) criteria.

Methods

Adult patients with a duration of SSc more than 3 years, a diffusing capacity of the lung for carbon monoxide less than 60% predicted, and no previous diagnosis of any form of pulmonary hypertension (PH) underwent screening tests followed by right heart catheterization. Subjects were divided into three groups: normal mPAP, BoPAP, and PAH. Exploratory comparative and binary logistic regression analyses were performed for the BoPAP versus normal mPAP and PAH versus BoPAP groups.

Results

Of 244 patients evaluated, 148 (60%) had normal mPAP, 36 (15%) had BoPAP, and 60 (25%) had definite PAH. Univariable logistic regression (ULR) showed the mean tricuspid regurgitation velocity in patients with BoPAP to be intermediate between normal mPAP and PAH. In the ULR analyses BoPAP versus normal mPAP and PAH versus BoPAP, the statistically significant predictors were, amongst others: demographic, clinical, pulmonary function, echocardiographic and hemodynamic variables.

Conclusions

In this exploratory post-hoc analysis of the DETECT study population patients with BoPAP could be distinguished from patients with normal mPAP and PAH, and it appears that BoPAP may be an intermediate stage on the continuum between normal PA pressures and PAH.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0493-1) contains supplementary material, which is available to authorized users.     

Lung hyperinflation and functional exercise capacity in patients with COPD – a three-year longitudinal study

Background

Lung hyperinflation contributes to dyspnea, morbidity and mortality in chronic obstructive pulmonary disease (COPD). The inspiratory-to-total lung capacity (IC/TLC) ratio is a measure of lung hyperinflation and is associated with exercise intolerance. However, knowledge of its effect on longitudinal change in the 6-min walk distance (6MWD) in patients with COPD is scarce. We aimed to study whether the IC/TLC ratio predicts longitudinal change in 6MWD in patients with COPD.

Methods

This prospective cohort study included 389 patients aged 40–75?years with clinically stable COPD in Global Initiative for Chronic Obstructive Lung Disease stages II-IV. The 6MWD was measured at baseline, and after one and 3 years. We performed generalized estimating equation regression analyses to examine predictors for longitudinal change in 6MWD. Predictors at baseline were: IC/TLC ratio, age, gender, pack years, fat mass index (FMI), fat-free mass index (FFMI), number of exacerbations within 12?months prior to inclusion, Charlson index for comorbidities, forced vital capacity (FVC), forced expiratory volume in 1?s (FEV₁), and light and hard self-reported physical activity.

Results

Reduced IC/TLC ratio (p?<?0.001) was a statistically significant predictor for decline in 6MWD. With a 0.1-unit decrease in baseline IC/TLC ratio, the annual decline in 6MWD was 12.7?m (p?<?0.001). Study participants with an IC/TLC ratio in the upper quartiles maintained their 6MWD from baseline to year 3, while it was significantly reduced for the patients with an IC/TLC ratio in the lower quartiles. Absence of light and hard physical activity, increased age and FMI, decreased FEV₁ and FVC, more frequent exacerbations and higher Charlson comorbidity index were also predictors for lower 6MWD at any given time, but did not predict higher rate of decline over the timespan of the study.

Conclusion

Our findings demonstrated that patients with less lung hyperinflation at baseline maintained their functional exercise capacity during the follow-up period, and that it was significantly reduced for patients with increased lung hyperinflation.

     

Primary respiratory disease in patients with systemic lupus erythematosus: data from the Spanish rheumatology society lupus registry (RELESSER) cohort

Background

The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort.

Methods

All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology [SER], cross-sectional phase) registry were retrospectively investigated for the presence of primary pleuropulmonary manifestations.

Results

In total 3215 patients were included. At least one pleuropulmonary manifestation was present in 31% of patients. The most common manifestation was pleural disease (21%), followed by lupus pneumonitis (3.6%), pulmonary thromboembolism (2.9%), primary pulmonary hypertension (2.4%), diffuse interstitial lung disease (2%), alveolar hemorrhage (0.8%), and shrinking lung syndrome (0.8%).In the multivariable analysis, the variables associated with the development of pleuropulmonary manifestation were older age at disease onset (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02–1.04), higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores (OR 1.03, 95% CI 1.00–1.07), the presence of Raynaud’s phenomenon (OR 1.41, 95% CI 1.09–1.84), secondary antiphospholipid syndrome (OR 2.20, 95% CI 1.63–2.97), and the previous or concomitant occurrence of severe lupus nephritis, (OR 1.48, 95% CI 1.12–1.95) neuropsychiatric manifestations (OR 1.49, 95% CI 1.11–2.02), non-ischemic cardiac disease (OR 2.91, 95% CI 1.90–4.15), vasculitis (OR 1.81, 95% CI 1.25–2.62), hematological manifestations (OR 1.31, 95% CI 1.00–1.71), and gastrointestinal manifestations, excluding hepatitis (OR 2.05, 95% CI 1.14–3.66). Anti-RNP positivity had a clear tendency to significance (OR 1.32, 95% CI 1.00–1.75; P = 0.054).The development of pleuropulmonary manifestations independently contributes to a diminished survival (hazard ratio of 3.13). However, not all complications will influence the prognosis in the same way. Whereas the occurrence of pleural disease or pulmonary thromboembolism has a minimal impact on the survival of these patients, the remaining manifestations have a major impact on mortality.

Conclusion

Except for pleural disease, the remaining respiratory manifestations are very uncommon in SLE (<4%). Pleuropulmonary manifestations independently contributed to a decreased survival in these patients.