BRONCHOALVEOLAR LAVAGE IN MIXED CRYOGLOBULINAEMIA ASSOCIATED WITH HEPATITIS C VIRUS

In order to evaluate the presence of an inflammatory processof the lower respiratory tract in patients with mixed cryoglobulinaemia(MQ associated with hepatitis C virus (HCV), bronchoalveolarlavage (BAL) was performed in 16 non-smoking females free ofclinical pulmonary symptoms and with normal chest roentgenograms.Pulmonary function tests including diffusion capacity for carbonmonoxide (DLCO) were also carried out. Thirteen healthy subjectswere evaluated as the control group. Patients with MC had alower percentage of alveolar macrophages (75% vs 92%, P = 0.001)and a higher percentage of lymphocytes (19.7% vs 7%, P = 0.001)than healthy controls. The percentage of CD3+ lymphocytes washigher in MC patients than in controls (86.57% vs 70%, P = 0.004).No significant differences in the percentage of CD4 +, CD8 +and CD 197+ lymphocytes, neutrophils and eosinophils were found.Pulmonary function tests showed significantly lower values offorced expiratory flow (FEF) 25–75 (P = 0.05) and DLCO(P = 0.05) in MC patients than in healthy controls. No correlationsbetween BAL results and pulmonary function tests were found.The 5 yr follow-up of five patients did not demonstrate deteriorationin lung function. Thus, BAL results indicate a subclinical T-lymphocyticalveolitis in MC HCV+ patients that is not associated with arisk of deterioration in lung function. KEY WORDS: Mixed cryoglobulinaemia, Hepatitis C virus, Bronchoalveolar lavage, Lymphocytic alveolitis     

Intravenous cyclophosphamide pulse therapy in interstitial lung disease associated with systemic sclerosis in a retrospective open-label study: influence of the extent of inflammation on pulmonary function

Interstitial lung disease (ILD) is the primary cause of death in patients with systemic sclerosis (SSc). It is thought that chronic inflammation is a key component in SSc-ILD. Treatment, such as cyclophosphamide (CYC), targets this inflammation. We hypothesized that treatment with CYC might be more effective in the inflammatory phase. Therefore, we analyzed whether the extent of inflammation, as assessed by the proportion of ground glass compared to fibrosis, SSc disease duration, the extent of ILD, or baseline diffusion capacity of the lungs (DLCO) <?60%, modifies the effect of intravenous CYC pulse therapy (750 mg/m²) on pulmonary function (as measured by FVC, DLCO) in SSc-ILD patients, after 12, 24, and 36 months. Consecutive patients with SSc-ILD receiving CYC pulses between 2003 and 2015 were included. Pulmonary function tests were performed at 0, 6, 12, 24, and 36 months. There were 75 patients included. Forced vital capacity (FVC) (86% of predicted) and DLCO (42% of predicted) were stable after 12, 24 and 36 months of follow-up (p?>?0.05). Forty-four patients completed 12 cycles of CYC. For the extent of ILD, proportion of ground glass compared to fibrosis, SSc disease duration, and baseline DLCO, there were no differences (all p?>?0.05) in the course of FVC and DLCO. Treatment with CYC followed by maintenance therapy stabilizes pulmonary function in patients with SSc-ILD over a 3-year period. The extent of ILD, proportion of ground glass, SSc disease duration, and baseline DLCO <?60% did not influence the effect of CYC on pulmonary function.     

Comparison of different measures of diffusing capacity for carbon monoxide (DLCO) in systemic sclerosis

In systemic sclerosis (SSc), impaired diffusing capacity for carbon monoxide (DLCO) can indicate interstitial lung disease (ILD), pulmonary hypertension (PH), and/or other disease manifestations, including anemia. We undertook this study to compare the various measures of DLCO in the setting of a complex disease like SSc. We analyzed the pulmonary function tests of a cohort of SSc subjects, as a whole and among subjects with isolated PH and ILD separately. Associations were assessed using Spearman correlation coefficients, Student’s t tests, and F tests by one-way ANOVA. P values <0.05 were considered statistically significant. This study included 225 subjects (mean age, 57 years; 88 % women; mean disease duration, 9.6 years; 32 % with diffuse disease, 44 % with ILD, and 17 % with PH). Mean percent predicted DLCO values were 75 % for DLCOsb and 83 % for DLCOrb. Adjustment for alveolar volume (VA) resulted in near normalization of both DLCOsb/VAsb (91 %) and DLCOrb/VArb (91 %). Subjects with ILD had significantly lower DLCOsb but not DLCOsb/VAsb, whereas those with PH had significantly lower DLCOsb and DLCOsb/VAsb. Among the various measures of DLCO, DLCOsb had the strongest and most consistent associations with clinical outcomes of interest. Adjusting for alveolar volume dampened the associations except with PH, with which DLCOsb/VAsb was more strongly associated than DLCOsb. Low DLCOsb is the most sensitive measure to detect abnormalities in gas exchange in SSc but reflects both parenchymal lung disease and pulmonary vascular disease. Low DLCOsb/VAsb is more specific for pulmonary vascular disease and should be the preferred measure of gas exchange in SSc.     

High‐dose prednisolone and bolus cyclophosphamide in interstitial lung disease associated with systemic sclerosis: a prospective open study

Aim: Currently, therapy for interstitial lung disease in patients with systemic sclerosis is unsatisfactory. A prospective open label study was conducted in a North Indian tertiary Institute to assess the efficacy of intermittent pulse cyclophosphamide (CYC) and high‐dose prednisolone in systemic sclerosis (SSc)‐related interstitial lung disease (ILD). Methods: Consecutive patients with SSc and ILD, diagnosed on spirometry, carbon monoxide diffusing capacity (DLCO) and high‐resolution computed tomography (HRCT) scan were treated. Pulmonary function tests were carried out at baseline and after 6 months. Patients received oral prednisolone 1 mg/kg body weight initially, with tapering to a dose of 7.5 mg/day was reached. Monthly CYC pulses were given for 6 months followed by 3‐monthly maintenance pulses. CYC was discontinued in patients with declining pulmonary function, adverse effects or static disease after 6 months. Results: Average disease duration of 36 patients was 59.78 ± 63.22 months. Seven patients improved (forced vital capacity [FVC] increase 10% or DLCO increase 15%), five deteriorated (FVC decline 10% or DLCO decline 15%) and 24 had stable disease. Thus, 31 out of 36 patients either improved or had static lung disease. Mean FVC (% of predicted) improved by 4.16% over 6 months (P = 0.069). Mean DLCO (% of predicted) improved by 5.66% (P = 0.27). Average % of predicted DLCO at baseline was 39%. Conclusion: High‐dose prednisolone with pulse CYC can either improve or stabilize lung functions in patients with severe systemic sclerosis lung disease irrespective of presence of ground glass appearance on HRCT.     

Pulmonary arterial hypertension in systemic sclerosis: the need for early detection and treatment

Pulmonary arterial hypertension (PAH) is an important cause of mortality in systemic sclerosis (SSc). The symptoms are non-specific and can be ascribed to other features of the disease, so it is often underrecognized until the late stages. Earlier treatment with new agents is associated with better treatment outcomes. The aim of this article is to develop evidence-based guidelines for screening for PAH and interstitial lung disease (ILD) in SSc. PAH occurs in up to 27% of patients with SSc. Abnormal pulmonary function, particularly a disproportionate fall in carbon monoxide diffusing capacity (DLCO), can identify patients in the early stages of PAH, prompting further investigation in high-risk patients (limited SSc of >10 years' duration, symptoms and/or signs of PAH, DLCO <50% predicted, a rapid or large fall in DLCO without evidence of ILD and/or estimated systolic pulmonary artery pressure >45 mmHg on echocardiography). Right heart catheter remains the diagnostic gold standard. An algorithm for screening with regular pulmonary function tests for the early detection of PAH and ILD in SSc is proposed.     

Pulmonary dysfunction due to combination of extra-pulmonary causes and alveolar damage is present from first the day of hospital admission in the early phase of acute pancreatitis

BackgroundOnly few studies have attempted to evaluate the pulmonary function in the early phase of acute pancreatitis (AP), although pulmonary dysfunction is the most frequent complication in the early phase of AP. We aimed to evaluate the changes in pulmonary function tests during the early phase of AP.MethodsProspective cohort study including 44 patients (52% men; median age 54 years) admitted with first attack of AP and 22 healthy controls. Patients underwent assessments on day 1, 2, 3, 6, and 10 as well as one month after discharge. Pulmonary function tests included the % predicted: forced expiratory volume during the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), diffusion lung capacity (DLCO) and the ratio between DLCO and alveolar volume (DLCO/VA).ResultsIn total, 9% developed severe acute pancreatitis, 7% died, and 14% required treatment at the intensive or semi-intensive care unit. From admission, patients had impaired FEV1, FVC, DLCO, and TLC compared with controls (p < 0.0001 in all analyses). Patients with CRP >150 mg/L had significantly lower lung function tests. One month after discharge, lung function tests improved but patients had lower FEV1 (p = 0.014), FVC (p = 0.022), TLC (p = 0.020), and DLCO (p < 0.001) compared with controls.ConclusionThis study found that patients with AP had evidence of pulmonary impairment from the first day after hospital admission. The impairment lasted several weeks after hospital discharge.     

The levels of serum-soluble Fas in patients with rheumatoid arthritis and systemic sclerosis

Different defects in Fas/APO-1 interaction with its ligand or in signaling of apoptosis may contribute to autoimmune disease. The aim of this study was to examine whether elevated serum-soluble Fas (sFas) levels are associated with rheumatoid arthritis (RA) or systemic sclerosis (SSc). sFas level was assayed using a sandwich ELISA in serum from 37 patients with RA, 30 patients with SSc and 20 healthy controls. The RA patients were classified according to disease activity, anatomical joint damage, and the presence of pulmonary involvement. Presence of pulmonary fibrosis, CO diffusion capacity (DLCO) and skin score were determined in patients with SSc. Serum sFas levels were not significantly different between study groups. Serum sFas level in the active RA patients was significantly higher than in the patients with inactive disease (p<0.05). The untreated active RA patients had significantly higher sFas level than healthy controls (p<0.05). In RA patients, sFas level was significantly correlated with rheumatoid factor titer (p=0.01), C-reactive protein (p<0.05), and erythrocyte sedimentation rate (p<0.05). The RA patients with severe joint damage had significantly higher sFas level than those with mild joint damage (p<0.05). The untreated SSc patients had significantly higher sFas levels than the treated SSc patients and healthy controls (p<0.01). Serum sFas level was not correlated with presence of pulmonary fibrosis, DLCO or skin score. The soluble Fas molecule may provide a useful additional marker for assessment of disease activity and severity in patients with RA.Abbreviations CRP C-reactive protein - DLCO CO diffusion capacity - ESR Erythrocyte sedimentation rate - RA Rheumatoid arthritis - RF Rheumatoid factor - sFas Serum-soluble Fas - SSc Systemic sclerosis     

Pulmonary dysfunction and hepatopulmonary syndrome in cirrhosis and portal hypertension

Background: Pulmonary dysfunction including the hepatopulmonary syndrome (HPS) is an important complication to cirrhosis and portal hypertension. However, the precise relation to liver dysfunction and the prevalence of HPS are unclear. Aims: We therefore aimed to assess (i) the prevalence of HPS in consecutive alcoholic cirrhotic patients, (ii) the degree of pulmonary dysfunction in relation to liver function and (iii) the response of a 100% oxygen test on cardiopulmonary and peripheral oxygenation. Methods: Fifty patients with cirrhosis and 12 matched healthy controls were entered in this study. All underwent haemodynamic and pulmonary investigations [lung diffusing capacity for carbon monoxide (DLCO), contrast‐enhanced echocardiography and detection of extrapulmonary shunt fraction]. A 100% oxygen test was performed with the assessment of arterial oxygen tension (PaO₂), the alveolar‐arterial oxygen gradient (AaPO₂) and peripheral transcutaneous oxygen tension (tcPO₂). Results: The prevalence of HPS was 10%. PaO₂ and DLCO were reduced in 32 and 72% and AaPO₂, was increased in 60% of the patients respectively. DLCO correlated with indicators of liver dysfunction (galactose elimination capacity, P<0.01, indocyanine green clearance, P<0.001), portal hypertension (post‐sinusoidal resistance, P<0.01) and central hypovolaemia (central and arterial blood volume, P<0.01). After 100% oxygen inhalation, the changes in PaO₂, AaPO₂, tcPO₂ and heart rate were abnormal in the patients compared with controls (P<0.02). Conclusions: Pulmonary dysfunction in alcoholic cirrhosis is common and relates to different aspects of liver dysfunction, whereas the prevalence of HPS is low. The haemodynamic response to oxygen inhalation is clearly impaired and HPS and pulmonary dysfunction seem to be caused by different pathophysiological mechanisms.     

High N‐terminal pro–brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis

Objective

To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc).

Methods

Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO /VA ) ratio and N‐terminal pro–brain natriuretic peptide (NT‐proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36‐month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea.

Results

Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan‐Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO /VA ratio <70% or <60% (P < 0.01 for each comparison), elevated plasma NT‐proBNP level (>97th percentile of normal; P = 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P = 0.08), and erythrocyte sedimentation rate >28 mm/hour (P = 0.015). In multivariate analyses, an elevated baseline NT‐proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69–62.42]) and a DLCO /VA ratio <60% (HR 36.66 [95% CI 3.45–387.6]) were predictors of the occurrence of PAH during followup. An increased NT‐proBNP level together with a decreased DLCO /VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90–450.33]).

Conclusion

This prospective study identified a decreased DLCO /VA ratio and an increased NT‐proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.

     

Isolated diffusing capacity reduction in systemic sclerosis.

OBJECTIVE. To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLCO) at the time of initial evaluation. METHODS. Patients with an isolated reduction in DLCO (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV1] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. RESULTS. An isolated reduction in DLCO, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLCO (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLCO of less than 55% of predicted normal and a FVC (% predicted)/DLCO (% predicted) ratio of greater than 1.4. Among all patients in whom this ratio was greater than 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was less than 1.4 (P less than 0.01). Of the 152 patients with isolated DLCO reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0-13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLCO demonstrated a significant improvement (greater than 20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. CONCLUSION. Isolated reduction in DLCO is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLCO (less than 55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.     

Effects of micronutrient antioxidants (alpha-tocopherol and ascorbic acid) on skin thickening and lung function in patients with early diffuse systemic sclerosis

To assess the effects of alpha-tocopherol and ascorbic acid on skin thickening and lung function in patients with early diffuse systemic sclerosis (SSc), thirteen patients with early diffuse SSc, with positive anti-topoisomerase-I antibody, high skin thickening progression rate (STPR ≥ 12/year) and decreased lung diffusing capacity (DLCO ≤ 75%) were included in this study. Patients were randomized into two subgroups: Subgroup A—six patients, treated with intravenous cyclophosphamide (CyP) (500 mg/m² of body surface monthly) and antioxidants (alpha-tocopherol 400 IU/day and ascorbic acid 1,000 mg/day), and Subgroup B—seven patients, who received CyP without antioxidants. In both subgroups, effects of treatment on skin thickening and lung function were evaluated by comparison of the modified Rodnan skin score (MRSS), STPR, forced vital capacity (FVC), transfer-factor (DLCO) and diffusing coefficient for carbon monoxide (DLCO/VA) at baseline and 1 month after the sixth pulse of CyP. The mean MRSS did not change from baseline to the end of the follow-up in subgroup A (15.7 vs. 16.4, P = 0.50), but it increased significantly in subgroup B (17.9 vs. 23.6, P = 0.03). Although the mean STPR decreased notably in both subgroups of patients (in subgroup A–from 18.9/year to 2.2/year, P = 0.03, and in subgroup B–from 17.5/year to 8.6/year, P = 0.03), the mean STPR at the end of the treatment period was significantly lower in subgroup A (2.2/year vs. 8.6/year, P = 0.04). The mean value of FVC did not change either in subgroup A (91.0–87%, P = 0.2) or in subgroup B (from 101.2 to 99.7%, P = 0.7). Parameters of lung diffusing capacity improved somewhat in subgroup A (DLCO from 55.7 to 62.0% and DLCO/VA from 68.7 to 74.2%) and decreased in subgroup B (DLCO from 66.2 to 60.6% and DLCO/VA from 76.9 to 71.6%), but differences were not statistically significant. After 6 months of therapy, patients treated with CyP and antioxidants had a significantly lower STPR, compared to patients treated with CyP only. Lung function parameters remained stable in both subgroups. However, lung diffusing capacity improved slightly, without statistical significance, in patients treated with CyP and antioxidants, and it deteriorated in patients without antioxidants.     

Isolated diffusing capacity reduction in systemic sclerosis

Objective. To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLco) at the time of initial evaluation. Methods. Patients with an isolated reduction in DLco (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV₁] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. Results. An isolated reduction in DLco, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLco (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLco of < 55% of predicted normal and a FVC (% predicted)/DLco (% predicted) ratio of > 1.4. Among all patients in whom this ratio was > 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was <1.4 (P < 0.01). Of the 152 patients with isolated DLco reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0–13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLco demonstrated a significant improvement (>20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. Conclusion. Isolated reduction in DLco is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLco (<55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.     

Validity of the Saint George's Respiratory Questionnaire in the evaluation of the health-related quality of life in patients with interstitial lung disease secondary to systemic sclerosis

Objectives. Interstitial lung disease (ILD) profoundly affectsthe health-related quality of life (HRQoL) in patients withsystemic sclerosis (SSc). We tested the validity of the SaintGeorge's Respiratory Questionnaire (SGRQ), a lung-specific HRQoL-evaluationtool, in a population of SSc patients with ILD. Methods. Twenty-eight consecutive SSc patients with a restrictivepulmonary involvement, defined as a forced vital capacity <80%of the predicted, with no pulmonary hypertension were considered.All the patients filled in the Medical Research Council (MRC)scale for perceived breathlessness, the SGRQ and the DisabilityIndex of the Health Assessment Questionnaire (HAQ DI), and underwentevaluation with complete pulmonary function testing (PFT), 6-minutewalk distance (6MWD) and high-resolution computed tomography(HRCT). Results. The SGRQ ‘activity’ scores inversely correlatedwith the 6MWD (r = –0.86, P < 0.001) and forced vitalcapacity percentage of predicted values (r = –0.47) anddirectly correlated with HRCT (r = 0.41, P < 0.05), MRC (= 0.64, P < 0.001) or HAQ DI scores (r = 0.62, P < 0.001),independently of disease duration or subset. On the contrary,HAQ DI scores were influenced by those variables and correctedcorrelations with 6MWD (r = 0.56, P < 0.001) or HRCT scores(r = 0.36, P = NS) were less strong than those observed withthe SGRQ. Conclusions. The SGRQ, although not specifically designed forscleroderma, is a valid respiratory-specific questionnaire forthe evaluation of HRQoL in patients with SSc-related ILD. TheSGRQ performs better in relation to exercise capacity and lungimaging than other non-respiratory-specific questionnaires widelyused in scleroderma studies. Further studies are needed to addressits ability to assess changes over time or in response to therapy. KEY WORDS: Systemic sclerosis, Quality of life, Interstitial lung disease Submitted 22 March 2006; revised version accepted 19 May 2006.     

Pulmonary survival study in 91 patients with systemic sclerosis

In systemic sclerosis (SSc), major determinant of morbidity and mortality is pulmonary complication including pulmonary interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). In this study, the natural course of pulmonary involvement in SSc patients was investigated. This was a historical cohort study of SSc patients at a referral center for SSc in Iran between February 1998 and December 2007. Patients had a standardized initial evaluation, and interstitial pulmonary involvement was established by high-resolution CT scan (HRCT). Pulmonary hypertension was assessed by tricuspid gradient on echocardiography. Development of abnormal FVC or DLCO was considered as secondary outcome. Analysis of pulmonary survival was performed for primary and secondary outcomes. Ninety-one SSc patients were included in the study with the mean age of 44.1 (14.8). Among these, 65 (71.4%) patients were classified as limited subtype (lcSSc) and 84 (93.3%) were women. PAH was investigated in 8 (8.2%) patients, 1 (6.7%) in dcSSc and 7 (15.9%) in lcSSc subtype of disease. ILD had developed after a median of 107 (SE = 24.4) months after the first symptom of SSc, and 29 patients (31.9%) developed pulmonary fibrosis. Alveolitis and fibrosis had developed after a median of 129.0 (22.9) and 259.0 (74.2) months, respectively. There was a significant difference in Alveolitis-free pulmonary survival between two subgroups of the disease, which showed pulmonary alveolitis developed later in limited SSc (P = 0.03). The difference was not significant in two subtypes when Cox regression model was used to identify the effect of other prognostic factors on pulmonary survival in patients. In the present study, clinical manifestations of two subtypes of disease were divergent at first; however they became convergent in late stages, and this was the same as results in previous studies. Echocardiography for evaluation of pulmonary hypertension and pulmonary function tests for early detection of ILD and PAH is recommended for SSc patients to detect early stages of pulmonary involvement before significant vascular and fibrotic changes occur.     

Two‐year experience with mycophenolate mofetil in patients with scleroderma lung disease: a case series

To assess the effect of mycophenolate mofetil (MMF) on pulmonary functions in patients with systemic sclerosis‐associated lung disease (SSc‐ILD) who experienced an inadequate response to first line cyclophosphamide (CYC) therapy. Twelve consecutive SSc‐ILD patients who received MMF due to inadequate response to CYC as a first line agent, were retrospectively reviewed. Over the course of 2 years, pulmonary function tests (PFT) and high‐resolution computed tomography (HRCT) scans were performed. Following initial baseline tests, PFTs were continued at a frequency of every 6 months and HRCT scans were performed every 12 months. After MMF treatment, values of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) improved in three (25%) and two (16.6%) patients, respectively. It is also noted that the evaluation of serial HCRT scans showed no change in 54.5% of patients. Our case series suggested that PFT and imaging scores seemed to be stabilized by MMF in SSc‐ILD patients who were inadequate responders to CYC.     

Screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension: A systematic review

Objective

Pulmonary arterial hypertension (PAH) is a frequent complication in connective tissue diseases (CTD), especially in systemic sclerosis (SSc), and is associated with a high degree of morbidity and mortality. We undertook a systematic review for the screening tests for CTD-PAH.

Methods

A systematic literature search of PAH in CTD was performed in available databases through June 2012. Our evaluation of diagnostic tests was focused on patients with PAH confirmed by right heart catheterization (RHC).

Results

The search resulted in 2805 titles and 838 abstracts. Our final inclusion encompassed 22 articles—six of which were case–control studies and 16 were cohort studies. Twelve studies assessed the tricuspid regurgitation velocity (VTR) or equivalent right ventricular systolic pressure (RVSP) using transthoracic echocardiogram (TTE) as a threshold for RHC in patients suspected as having PAH. The screening threshold for RHC was VTR from >2.73 to >3.16 m/s without symptoms or 2.5–3.0 m/s with symptoms and resulted in 20–67% of patients having RHC-proven PAH. Three studies looked at pulmonary function tests and found that a low lung diffusing capacity for carbon monoxide (DLCO) (45–70% of predicted) is associated with a 5.6–7.4% development of PAH, and a decline in DLCO% is associated with an increase in the specificity (for DLCO ≤60%, spec = 45%; and for DLCO ≤50%, spec = 90%) for PAH. Five studies assessed N-terminal prohormone of brain natriuretic peptide (NT-ProBNP), where a cutoff >239 pg/ml had a sensitivity of 90–100%.

Conclusions

Our systematic review revealed that most evidence exists for TTE, pulmonary function tests, and NT-ProBNP for screening and diagnosis of SSc-PAH; however, more robust studies are needed.     

Serum IL-33 levels are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis

To determine serum interleukin-33 (IL-33) levels and their associations with clinical parameters in patients with systemic sclerosis (SSc). Serum IL-33 levels were examined by enzyme-linked immunosorbent assay in 69 patients with SSc and 30 healthy individuals. In a retrospective longitudinal study, sera from 14 patients with SSc were analyzed (follow-up, 1–7 years). Serum IL-33 levels were elevated in SSc patients (261.7 ± 141.9 pg/ml) compared with healthy individuals (174.9 ± 72.4 pg/ml; P < 0.001). Patients with diffuse cutaneous SSc had higher levels of IL-33 (287.5 ± 146.6 pg/ml) than those with limited cutaneous SSc (221.5 ± 126.5 pg/ml; P < 0.05). Pulmonary fibrosis and decreased forced vital capacity were more commonly found in patients with elevated IL-33 levels than in those with normal IL-33 levels. IL-33 levels correlated positively with the extent of skin sclerosis, and inversely with percent predicted forced vital capacity. IL-33 levels were increased in SSc patients and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. Therefore, IL-33 possibly plays a role in cutaneous and pulmonary fibrosis in SSc patients.     

Pulmonary function abnormalities in chronic severe cardiomyopathy preceding cardiac transplantation.

Pulmonary function data, including diffusing capacity, were evaluated in 56 patients with chronic severe cardiomyopathy before heart transplantation. Cardiac catheterization data were used to describe the relationship between cardiac and pulmonary function. Of 56 patients 44 had some abnormality in pulmonary function. The majority, 30 of 56, had a restrictive impairment alone. Of 28 patients in whom diffusing capacity was measured, 64% had a diffusion impairment. There was no association of pulmonary function impairment with type of cardiomyopathy or smoking history. Pulmonary capillary wedge pressure correlated positively with DLCO, but not with FVC or TLC. Cardiac index and ejection fraction did not correlate with diffusing capacity. This precardiac transplantation cardiomyopathy patient group demonstrated frequent pulmonary function abnormalities not previously recognized.     

Effect of mycophenolate sodium in scleroderma-related interstitial lung disease

This study aims to determine the effectiveness of mycophenolate sodium (MS) in patients with scleroderma (SSc)-related interstitial lung disease (ILD). In a prospective observational study, we evaluated 14 consecutive SSc-ILD patients who were treated with MS for 12 months. The effect of MS on lung function was examined by using longitudinal data analytic methods. Wilcoxon rank–sum tests were used to examine the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) by pulmonary function testing. As a group, the median values for FVC, FEV1 and DLCO did not change significantly after 12 months of MS therapy and fulfilled the definition of stable disease by the American Thoracic Society. Individually, after 12 months of treatment, 6 out of 14 patients showed a pulmonary improvement defined as an increase of more than 10% in FVC, and 5 out of 14 patients remained stable. By contrast, the median FVC had declined a non-significant 7.2% from the previous 12 months before MS initiation. No significant drug adverse effects were registered. These prospective data suggest that MS is a safe and well-tolerated therapy for SSc-ILD patients, and it is capable of preventing functional pulmonary deterioration.