Physiological predictors of survival in patients with sarcoidosis-associated pulmonary hypertension: results from an international registry.

INTRODUCTION: Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with reduced survival in single-centre studies. The international Registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients. METHODS: ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrolment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest radiography, Scadding stage and 6-min walk distance (6MWD), among others. Cox regression models were used to identify independent predictors of transplant-free survival. RESULTS: Data from 215 patients followed for a mean±sd 2.5±1.9 years were available for analysis. In the 159 precapillary patients, the Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival was 89.2%, 71.7% and 62.0%, respectively. Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival in the incident group was 83.5%, 70.3% and 58.3%, respectively, and in the prevalent group was 94.7%, 72.2% and 66.3%, respectively. Patients with reduced diffusing capacity of the lung for carbon monoxide (D LCO) (<35% predicted) and 6MWD <300 m in the precapillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio were identified as independent risk factors for reduced transplant-free survival in the precapillary cohort. CONCLUSION: Reduced D LCO (<35% pred) and 6MWD (<300 m) at the time of registry enrolment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV1/FVC ratio was identified as an independent risk factor for worsened outcomes.

Can computed tomography and carbon monoxide transfer coefficient diagnose an asthma-like phenotype in COPD?

BACKGROUND AND OBJECTIVE: Post-mortem and computed tomography (CT) studies indicated that emphysema is a feature of COPD even in the 'blue bloater/chronic bronchitis' type. We aim to test the hypothesis that the non-emphysematous patients are distinct from the main body of COPD and are more akin to asthmatic patients. METHODS: We studied 54 patients with COPD. Emphysema was measured by Goddard's visual scoring of CT scan and the carbon monoxide transfer coefficient (KCO). Bronchial biopsy was offered for thickness of basement membrane (BM) (≥7 µm) as a marker of remodelling in irreversible asthma. Spirometry was repeated after therapy with Budesonide/Formoterol for 1 year. RESULTS: The non-emphysematous phenotype were 24 of 54 patients (44%) by CT scan and 23 of 54 patients (43%) by KCO, showing agreement in 53 out of 54 patients. The non-emphysematous patients were younger, had higher forced expiratory volume in 1 s (FEV1 ) (median 61% vs 49.7%), greater prevalence of hypertrophy of nasal turbinates and higher serum IgE. The emphysematous phenotype had lower BMI and greater dyspnoea score. The BM was thickened in 11 of 14 and 0 of 10 patients in the non-emphysematous and emphysematous groups, respectively. Three patients without emphysema and a normal BM normalized their FEV1 upon receiving inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA). All the non-emphysematous improved their FEV1 after ICS/LABA (median = 215 mL). The median decline in the emphysematous was -65 mL. CONCLUSION: The non-emphysematous phenotype of COPD displays important features of asthma: clinical picture, histology and response to ICS. CT and KCO can predict spirometric response to ICS/LABA.

Cytokine gene polymorphisms and serum cytokine levels in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Studies have demonstrated associations between cytokine gene polymorphisms and the risk of idiopathic pulmonary fibrosis (IPF). We therefore examined polymorphisms in the genes encoding interleukin (IL)-6, IL-10, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and transforming growth factor-beta 1 (TGF-ß1), and compared the serum levels of these cytokines in IPF patients and healthy controls. Furthermore, we examined the association of the studied genotypes and serum cytokine levels with physiological parameters and the extent of parenchymal involvement determined by high-resolution computed tomography (HRCT). METHODS: Sixty patients with IPF and 150 healthy controls were included. Cytokine genotyping was performed using the polymerase chain reaction sequence specific primer (PCR-SSP) method. In a subset of patients and controls, serum cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: There was no difference between IPF patients and controls in the genotype and allele distributions of polymorphisms in TNF-α, IFN-γ, IL-6, IL-10, and TGF-ß1 (all p > 0.05). The TNF-α (-308) GG, IL-6 (-174) GG and CG, and IL-10 (-1082, -819, -592) ACC ATA genotypes were significantly associated with HRCT scores (all p < 0.05). IL-10 (-1082, -819, -592) ACC haplotype was associated with the diffusion capacity of the lung for carbon monoxide, and ATA haplotype was associated with the partial pressure of oxygen (PaO2) (all p < 0.05). The TGF-ß1 (codons 10 and 25) TC GG, TC GC, CC GG and CC GC genotypes were significantly associated with the PaO2 and HRCT scores (p < 0.05). The TGF-ß1 (codons 10 and 25) CC GG genotype (5 patients) was significantly associated with higher PaO2 value and less parenchymal involvement (i.e., a lower total extent score) compared to the other TGF-ß1 genotypes (81.5 ± 11.8 mm Hg vs. 67.4 ± 11.1 mm Hg, p = 0.009 and 5.60 ± 1.3 vs. 8.51 ± 2.9, p = 0.037, respectively). Significant differences were noted between patients (n = 38) and controls (n = 36) in the serum levels of IL-6 and IL-10 (both, p < 0.0001), but not in the levels of TNF-α and TGF-ß1 (both, p > 0.05). CONCLUSION: The studied genotypes and alleles do not predispose to the development of IPF but appear to play an important role in disease severity. Our results suggest that the TGF-ß1 (codons 10 and 25) CC GG genotype could be a useful genetic marker for identifying a subset of IPF patients with a favorable prognosis; however, validation in a larger sample is required.

Single nucleotide polymorphisms in cytokine genes and their association with primary Sjögren's syndrome in Saudi patients: A cross-sectional study.

OBJECTIVES: To determine the allelic frequencies and effects of genotypic variations in cytokine gene polymorphisms in a Saudi Arabian population. METHODS: This cross-sectional study involved 41 patients with Primary Sjögren's syndrome (pSS) and 71 healthy controls between October 2018 and May 2019. Single nucleotide polymorphisms genotyping was performed using the SEQUENOM MassARRAY® System, targeting nine polymorphisms in different cytokine genes. Chi-square tests were used to compare the patients and controls. RESULTS: The interleukin-1 beta (IL-1ß) rs1143627 CT (control, 52.7%; patients, 21.2%) and TT + CT (p= 0.003; p=0.033) genotypes were less frequent in patients with pSS than in healthy controls. The C allele in rs10488631 in the interferon regulatory factor 5 (IRF5) gene and the A allele in rs12583006 in the B-cell activating factor (BAFF) gene were associated with an increased risk of pSS development in the patient group. CONCLUSION: The CT genotype at -31 (rs1143627) in the IL-1ß gene was not associated with a high risk of pSS development in the Saudi population, in contrast to what has been verified in other ethnicities. However, the C allele in rs10488631 in IRF-5 and the A allele in rs12583006 in BAFF were associated.

Association of Inflammatory Cytokine Levels with Extra Glandular Manifestations, Fatigue, and Disease Activity in Primary Sjögren's Syndrome in Saudi Patients: A Cross-Sectional Study.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease that can cause fatigue and extraglandular manifestations (EGMs). pSS is associated with cytokine network dysregulation, which may be related to the immune-mediated destruction of exocrine glands. OBJECTIVE: We determined cytokine levels and their relationship to EGMs, the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI), and fatigue in Saudi patients with pSS. METHODS: This study was a cross-sectional, single-center study. We included forty-one patients and 71 controls. Serum samples were collected from random healthy people and pSS patients who were followed in the rheumatology and pulmonary clinics of King Saud University Medical City in Riyadh, Saudi Arabia. Levels of the frequently studied cytokines were measured using Luminex xMAP technology. Each ESSDAI score and EGM were recorded, and the Arabic version of the fatigue severity scale (FSS) was applied to assess fatigue. The main outcome measures were cytokine levels in pSS Saudi patients using/not using immune-suppressive medications (ISMs). RESULTS: Thirty-six (87.8%) patients had one or more EGMs, and the mean ESSDAI score was 9.95 ± 7.73. There was a significant decrease in TNFα and IL-21 levels in the pSS group compared to those in the control group (p = 0.034 and p < 0.001, respectively), whereas IL-12 levels were significantly elevated in the pSS group (p = 0.002). Cytokine levels in patients who used ISMs were the same as those in patients who did not use medications. Decreased IL-1ß (p = 0.014), IL-2 (p = 0.035), IL-6 (p = 0.014), and IL-35 (p = 0.010) levels were observed in patients who had EGMs. Patients who had low disease activity exhibited low IL-10 (p = 0.018) and high IFN-α (p = 0.049), IFN-ß (p = 0.049), IL-1ß (p = 0.006), and IL-35 (p = 0.032) levels compared to patients with high disease activity. A negative association between a positive fatigue score and IL-1ß (p = 0.010), IL-2 (p = 0.037), IFN-α (p = 0.025), TNFα (p = 0.030), IL-17 (p = 0.029), IL-12 (p = 0.046), and IL-21 (p = 0.005) levels was found. CONCLUSIONS: Cytokine profiles correlate with EGMs, ESSDAI, and fatigue. Patients with controlled disease activity have a normal cytokine profile that is similar to that of controls.

Pulmonary hemodynamics and transplant-free survival in sarcoidosis-associated pulmonary hypertension: Results from an international registry.

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan-Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant-free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.

The six-minute walk test in sarcoidosis associated pulmonary hypertension: Results from an international registry.

INTRODUCTION: Sarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation. MATERIAL AND METHODS: ReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR). FINDINGS: 174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300 m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300 m (p = 0.012). No associations with outcome were observed with mDSP cutoff 200 m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p = 0.001), DLCO% (p = 0.0001) and sPAP (p = 0.031) on multivariate analysis. These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p = 0.015). CONCLUSION: Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis.

Echocardiographic estimate of pulmonary artery pressure in sarcoidosis patients - real world data from a multi-national study.

INTRODUCTION: Echocardiographic measurement of the right ventricular systolic pressure (RVSP) is commonly used for estimating systolic pulmonary artery pressure (PASP) measured during right heart catheterization (RHC) in patients suspected for pulmonary hypertension (PH). Generally, there seems to be a strong correlation. However, this has been reported as less robust in sarcoidosis. We aim to investigate the correlation between RVSP and RHC measurements using real world data and analyzed factors influencing the relationship between RVSP and PASP in sarcoidosis. METHODS & RESULTS: Data of patients with and without sarcoidosis associated PH who had both a measurable echocardiographic RVSP and invasive PASP were collected from the RESAPH registry, PULSAR study and Cincinnati Sarcoidosis Clinic database (n=173, 60.1% female, mean age 56.0±9.5 years). Among them, 124 had PH confirmed by RHC. There was a strong correlation between RVSP and PASP (r=0.640). This correlation was significant in both male and female, white or non-white, forced vital capacity (FVC) >60%, and presence of fibrosis (p<0.001). However, it was less robust in patients with FVC of 50% or less. RVSP was considered inaccurate if the difference with PASP was > 10mmHg. Inaccurate echocardiographic estimation of the invasive PASP occurred in 50.8%, with overestimation mostly in patients without PH, and underestimation in patients with severe PH. An RVSP>50mmHg was associated with worse survival. CONCLUSIONS: In this real world multicenter cohort of sarcoidosis patients, we found a significant correlation between RVSP as determined by echocardiography and invasive PASP. Over- or underestimation of PASP occurred frequently. Therefore, echocardiographic RVSP measurement alone to screen for PH in sarcoidosis should be used with caution.

Prediction of pulmonary hypertension in patients with or without interstitial lung disease: reliability of CT findings.

PURPOSE: To study the reliability of pulmonary vascular measurements based on computed tomography (CT) in the prediction of pulmonary hypertension (PH) in patients with advanced interstitial lung disease (ILD) compared with those without ILD. MATERIALS AND METHODS: The study was approved by the Institutional Review Board. All patients gave written informed consent. A prospective study of 134 patients who underwent right-sided heart catheterization and chest CT scanning within 72 hours of admission was conducted. Patients were divided into two groups-one with ILD (group A, n = 100) and one without ILD (group B, n = 34). CT measurements of the main pulmonary artery diameter (PAD), the ratio of PAD to the ascending aorta diameter (AAD), right pulmonary artery diameter (RPAD), and left pulmonary artery diameter (LPAD) were obtained. Univariate logistic regression analysis was performed, and receiver operating characteristic curves were constructed to assess the predictive ability of vascular measurements obtained by using CT in the identification of PH. RESULTS: Main PAD was significantly greater in patients with PH than in those without PH in both groups (group A, P = .008; group B, P = .02). A PAD greater than 25 mm in patients with ILD was predictive of PH, with a sensitivity of 86.4% (32 of 37), a specificity of 41.2% (26 of 63), a positive predictive value of 46.3% (32 of 69), and a negative predictive value of 83.8% (26 of 31). In patients without ILD, a PAD greater than 31.6 mm and an LPAD greater than 21.4 mm were predictive of PH (sensitivity, 47.3% [nine of 19]; specificity, 93.3% [14 of 15]; positive predictive value, 90.0% [nine of 10]; and negative predictive value, 58.3% [14 of 24]). CONCLUSION: CT-derived vascular measurements were of limited utility in the prediction of PH in patients with ILD compared with those without ILD.

Asthma masquerading as chronic obstructive pulmonary disease: a study of smokers fulfilling the GOLD definition of chronic obstructive pulmonary disease.

BACKGROUND: Irreversible airways obstruction in smokers is usually attributed to chronic obstructive pulmonary disease (COPD). We speculate that some of these are cases of asthma indistinguishable from COPD. OBJECTIVES: To determine the prevalence of asthma in a 'COPD' population and how to differentiate the two conditions. METHODS: This was a prospective observational study of smokers fulfilling the Global Initiative for Chronic Obstructive Lung Disease definition of COPD [mean post-salbutamol forced expiratory volume in 1 s (FEV1) 66.9% predicted]. They were classified into 4 groups, as follows: (1) inhaled corticosteroid (ICS)-responsive asthma, defined by normalization of spirometry upon ICS treatment; (2) irreversible asthma, defined as airway obstruction for 1 year and bronchial biopsy indicating asthma; (3) COPD, in the presence of bilateral panlobular emphysema with bullae on high-resolution computed tomography, hypercapneic respiratory failure or bronchial biopsy indicating COPD, and (4) unclassified airflow limitation (AFL). RESULTS: Eighty patients fulfilled the definition of COPD. The initial diagnosis was COPD in 57.5% and asthma in 42.5%. The final diagnosis was ICS-responsive asthma in 48 patients (60%), irreversible asthma in 8 (10%), COPD in 16 (20%) and unclassified AFL in 8 (10%). A normal transfer coefficient for carbon monoxide (KCO) and an FEV1 fluctuation ≥18% during 1 year of follow-up distinguished irreversible asthma and COPD. Seven of the 8 patients with irreversible asthma had improved FEV1 at the end of 1 year (median 320 ml compared with -29 ml in COPD). Five out of the 8 unclassified AFL cases had normal KCO and a large improvement in FEV(1) suggestive of irreversible asthma. CONCLUSIONS: COPD, even in heavy smokers, includes cases of asthma. FEV1 fluctuation during 1 year is a novel concept which may distinguish irreversible asthma and COPD.

Acute exacerbation in interstitial lung disease.

BACKGROUND: Information regarding acute exacerbation (AE) in patients with interstitial lung disease (ILD) is limited. OBJECTIVES: The objective of the study was to elucidate the clinical features and outcome of AE among ILD patients. METHODS: We retrospectively analyzed the data of 667 consecutive ILD (nonidiopathic pulmonary fibrosis [IPF] ILD, n = 463; IPF, n = 204) patients. ILD patients meeting the 2016 definition of AE-IPF were identified. Information analyzed included pulmonary function tests, 6-min walk tests, and right heart catheterization data, among others. Cox regression models were used to identify independent predictors of survival. RESULTS: AE was identified in non-IPF ILD (n = 113) and IPF (n = 74). Compared with AE-IPF patients, non-IPF ILD patients with AE were of younger age, predominantly women, and primarily nonsmokers (all, P < 0.0001). The estimated survival probabilities at 1, 3, and 5 years were 88%, 75%, and 70%, respectively, in the ILD without AE group; 80%, 57%, and 50%, respectively, in the non-IPF ILD with AE group; and 53%, 38%, and 28%, respectively, in the AE-IPF group (P < 0.0001 by log-rank analysis). Age, body mass index, IPF diagnosis, AE, diffusion capacity of the lung for carbon monoxide <35% predicted, 6-min walk distance <300 meters, and cardiac index were independent predictors of survival in the ILD cohort. CONCLUSIONS: Non-IPF ILD patients with AE have distinct clinical features compared to AE-IPF patients. Importantly, AE is one of many independent risk factors associated with worsened outcomes regardless of the underlying ILD type.

Disease phenotype and diagnostic delay in Saudi patients with primary Sjögren's syndrome: An exploratory cross-sectional study.

OBJECTIVES: To describe primary Sjögren's syndrome (pSS) cohort in Saudi Arabiain view in of clinical/serological/histopathological phentotype, and, diagnostic delay. METHODS: A cross-sectional study conducted between October 2018 and May 2019. Diagnostic delay was calculated from symptoms onset to clinical diagnosis. The European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) were calculated. RESULTS: Forty-one patients were included in the study. There were predominantly females (78%) with a mean (±SD) age of 58.76±12.7 and disease duration of 4.6±2.28 years. The mean diagnostic delay was 2.2±2.4 (range 1-11) years. Minor salivary gland biopsy was performed on 38 (92.7%) patients with a mean focus score of 2.3± 1.2 points. Interstitial lung disease and arthritis were the most common extra-glandular manifestations (EGM) affecting 27 (65.9%) patients for both. The mean ESSDAI was 9.95±7.73 and ESSPRI was 5.17±2.4. CONCLUSION: Saudi primary Sjogren's syndrome patients have a high prevalence of EGM predominantly arthritis and ILD. The diagnostic delay is variable in our cohort.

Clinical characteristics and outcomes in patients with primary Sjogren's syndrome-associated interstitial lung disease.

BACKGROUND: Diagnosing primary Sjogren's syndrome (pSS)-associated interstitial lung disease (ILD) is complex and can be very challenging. In addition, information about the prognostic factors is limited. AIMS: We aimed to determine the clinical characteristics and prognostic factors that impact pSS-ILD survival. METHODS: This retrospective review included 84 consecutive patients diagnosed with pSS-ILD. The information analyzed included the clinical characteristics, laboratory findings, and physiological and hemodynamic data. Prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: The mean age was 60.5 years, and 61.9% were females. The mean time between the onset of symptoms and diagnosis was 21 months (range, 1-98 months). Minor salivary gland biopsy (MSGB) was positive for pSS in 92.3% of the cohort. Fifty percent of the patients had negative autoimmune serology related to pSS. Based on the available hemodynamic data, 40% had pulmonary hypertension (PH), and 20% had severe PH. During follow-up, acute exacerbation was noted in 38% of the cohort. The 5-year survival rate for all patients was 56%. Male sex, usual interstitial pneumonia pattern, and a reduced forced vital capacity were independent predictors of mortality in the pSS-ILD patients. CONCLUSIONS: A significant delay between the onset of symptoms and diagnosis was noted in our cohort. Importantly, our study highlights the importance of MSGB and emphasizes that clinicians should not rely solely on serological tests to diagnose pSS in ILD patients. The overall survival was poor, and more efforts are needed to diagnose pSS-ILD at an early stage and refer patients to experienced centers.

Outcome measures of the 6 minute walk test: relationships with physiologic and computed tomography findings in patients with sarcoidosis.

BACKGROUND: We assessed the relationship between physiologic parameters, computed tomography patterns, 6 minute walk distance (6MWD) and the distance-saturation product [DSP; defined as the product of the 6MWD and the lowest oxygen saturation during the 6 minute walk test (6MWT)]. In addition, we investigated factors affecting 6MWD in patients with pulmonary sarcoidosis. METHODS: We performed a retrospective study of patient demographics, treatment, pulmonary function, 6MWT, echocardiography and computed tomography results. RESULTS: Fifty nine patients were included in this study. Their mean+standard deviation age was 47.5 years + 12.5 years, and 42 (71.2%) were female. Mean pulmonary function parameters for forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and total lung capacity (TLC) results, as percentages of predicted values, were 77.6 +/- 22.2, 77.1 +/- 22.8 and 78.7 +/- 16.1, respectively. Comparison of the DSP with distance walked revealed a significant correlation with factors underlying reduced 6MWD, including gender, pulmonary function indices, partial pressure of oxygen (PaO2), and Borg dyspnea score. Other factors were significantly associated with DSP but not distance; these included lung fibrosis (p = 0.02), pulmonary hypertension (p = 0.01) and systemic therapy (p = 0.04). Backward elimination stepwise multiple regression analysis revealed that gender, and FEV1 were independent predictors of 6MWD, but FEV1 was more strongly related when DSP applied [DSP, R2 = 0.53, p = 0.02; distance, R2 = 0.45, p < 0.0001]. CONCLUSION: Our findings reveal that, compared to 6MWD alone, the DSP is correlated with a greater number of factors associated with reduced 6MWT performance. Therefore, the DSP may be a useful indicator of functional status in patients with sarcoidosis. Additional large-scale studies are warranted to validate our findings.

Predictors of mortality in interstitial lung disease patients without pulmonary hypertension.

BACKGROUND: There is a paucity of information regarding prognostic factors associated with reduced survival in interstitial lung disease (ILD) patients without pulmonary hypertension (PH). AIMS: The aim of this study was to determine physiological and hemodynamic parameters that impact survival among ILD patients without PH based on right heart catheterization (RHC). METHODS: Consecutive ILD patients who underwent RHC (n = 169) at one center were included. The information analyzed included demographics and physiological and hemodynamic parameters. Cox regression models were used to identify independent predictors of survival. RESULTS: The mean age was 55.0 years, and 49.7% of the patients were females. Thirty-three patients died, and two underwent transplantation. Patients with predicted diffusion capacity of the lung for carbon monoxide <35%, walking distance <300 m, and 6-min walk test (6MWT) final oxygen saturation measured by pulse oximetry (SpO 2) <85% were significantly associated with an increased mortality risk (P = 0.022, P < 0.0001, and P = 0.049, respectively; all by log-rank analysis). Advanced age, idiopathic pulmonary fibrosis diagnosis, reduced forced vital capacity, and low cardiac index were independent predictors of increased mortality in the ILD cohort. CONCLUSIONS: Our study demonstrates that parameters obtained from baseline pulmonary function tests and 6MWTs are important determinants of survival in ILD patients without PH. Importantly, cardiac index was the only hemodynamic variable independently associated with survival. Thus, in the absence of PH, when ILD patients perform poorly during the 6MWT manifested as reduced walking distance and desaturation at the end of the test, cardiovascular impairment must be ruled out.

Predictors of Mortality in Patients with Interstitial Lung Disease-Associated Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a well-established complication in interstitial lung disease (ILD) patients. The aim of this study is to investigate the physiological and hemodynamic parameters that predict mortality in patients with ILD-PH. METHODS: Consecutive ILD patients who underwent right heart catheterization (n = 340) were included. The information analyzed included demographics and physiological and hemodynamic parameters. Cox regression models were used to identify independent predictors of survival. RESULTS: In total, 96 patients had PH and an additional 56 patients had severe PH. The overall survival of idiopathic pulmonary fibrosis (IPF) patients with PH was significantly worse than the survival of patients with other types of ILD with PH (p < 0.0001 by log-rank analysis). Patients with a reduced diffusing capacity of the lung for carbon monoxide (DLco) (<35% predicted), six-minute walk test final oxygen saturation by pulse oximetry (SpO2) <88% and pulmonary vascular resistance ≥4.5 Wood units in the ILD-PH cohort had significantly worse survival. IPF diagnosis, forced vital capacity, DLco, systolic pulmonary artery pressure and cardiac index were identified as independent predictors of survival among the ILD-PH cohort. CONCLUSIONS: Patients with ILD-PH have poor prognosis. Physiological and hemodynamic parameters were important factors independently associated with outcome.

Clinical characteristics, comorbidities, and outcomes in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a common subtype of interstitial lung disease (ILD). Information about the associated comorbidities and predictors of survival among Saudi patients with IPF is limited. AIMS: The aim of the study was to determine the clinical characteristics, associated comorbidities, and prognostic factors that impact IPF survival. METHODS: Consecutive IPF patients diagnosed in our ILD center were included. The information analyzed included demographics, physiological parameters, and associated comorbidities, among others. Cox regression models were used to identify independent predictors of survival. RESULTS: The data of 212 patients with IPF were available for the analysis. The mean age was 66.4 years, and 70.8% were male. The mean time between the onset of symptoms and diagnosis was 11.6 months (range: 1-48 months). Common comorbid conditions noted in the IPF cohort included pulmonary hypertension (49.6%), diabetes mellitus (43.2%), hypertension (42.2%), osteoporosis (40.4%), and gastroesophageal reflux disease (32.1%). Acute exacerbation (AE) was noted in 21.2% of the IPF patients. AE, final saturation <85%, walking distance <300 m, and antifibrotic therapy were independent predictors of survival. CONCLUSIONS: In our IPF cohort, we found that there was a significant delay between the onset of symptoms and diagnosis. Moreover, we identified multiple comorbidities associated with IPF, which increases the burden on both IPF patients and clinicians. Importantly, AE and the use of antifibrotic therapy were independent predictors of survival. It is of paramount importance for clinicians to diagnose IPF at an early stage, refer patients to experienced centers, recognize comorbidities, and initiate antifibrotic therapy regardless of the underlying disease severity.

Clinical significance of minor salivary gland biopsy in patients with idiopathic interstitial pneumonia.

BACKGROUND: Significant overlap may occur between idiopathic interstitial pneumonia (IIP) and connective tissue diseases (CTDs) that do not meet the established classification criteria for any known CTDs (i.e., occult CTD). Performing minor salivary gland biopsy (MSGB) to detect occult primary Sjogren's syndrome (pSS) in IIP patients is not well studied. METHODS: Consecutive IIP patients underwent MSGB to determine the prevalence of positive MSGB findings. Furthermore, we characterised the clinical, physiological and serological profiles of the MSGB-positive patients. Cox regression models were used to identify independent predictors of survival. RESULTS: The data of 155 patients with IIP were available for analysis. Sixty patients (38.7%) had positive MSGB findings. Of them, the mean age was 63.3 years, 51.6% were women, usual interstitial pneumonia (UIP) was the predominant pattern (63.3%), and seronegative antibodies (61.6%) were likely. Patients with positive MSGB findings had significantly greater survival than those with negative MSGB findings (p = 0.041). After stratifying the MSGB cohort based on the presence of a UIP pattern, no significant difference in survival was noted between those with positive MSGB-UIP pattern and those with a negative MSGB-UIP pattern (p = 0.231). Multivariate analysis on all UIP patients showed that higher forced vital capacity (p = 0.010) and smoking status (p = 0.035) were independently associated with survival. CONCLUSIONS: A substantial number of IIP patients had underlying occult CTD, highlighting the importance of performing MSGB to identify the salivary component of pSS when evaluating patients with interstitial lung disease of undetermined aetiology.

Fatigue in Saudi Patients with Primary Sjögren's Syndrome and Its Correlation with Disease Characteristics and Outcome Measures: A Cross-Sectional Study.

BACKGROUND: Fatigue is a prevalent symptom affecting primary Sjögren's syndrome (pSS) patients. The purpose of this study is to determine the prevalence of fatigue in Saudi pSS patients and its correlation with disease features and outcome measures using a validated tool. METHODS: This is a cross-sectional study evaluating fatigue in pSS using the Arabic version of the fatigue severity scale (FSS). The EULAR Sjögren's syndrome disease activity index (ESSDAI) and EULAR Sjögren's syndrome patient reported index (ESSPRI) were calculated. RESULTS: Forty-one patients met the sample criteria and were involved in the final report. There were predominantly females (78%) with a mean (±SD) age and disease duration of 58.76±12.7 and 4.6±2.28 years, respectively. Based on the FSS, 18 (43.9%) patients had a positive test with a mean score of 5.43±0.76. The mean ESSDAI was 9.95±7.73, while the mean EESPRI was 5.17±2.4 with individual component scores were dryness (5.23±2.62), fatigue (5.4±2.88), and pain (4.88±3.31). The FSS had a significant correlation with PGA (r=0.559; p<0.001), PhGA (r=0.671; p<0.001), ESSDAI (r=0.402; p=0.01), ESSPRI fatigue component (r=0.0.621; p<0.001), ESSPRI pain component (r=0.558; p<0.001), and missed significance for the ESSPRI dryness component (r=0.289; p=0.071). There was no correlation between the total ESSPRI score and presence of fatigue (r=-0.261; p=0.104) nor the FSS score (r=-0.136; p=0.409). CONCLUSION: Fatigue is prevalent in Saudi pSS patients. FSS correlated with ESSDAI and ESSPRI components but not its total score signaling other unmeasured factors contributing to fatigue development.

Endobronchial biopsy in the final diagnosis of chronic obstructive pulmonary disease and asthma: a clinicopathological study.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are chronic conditions with an increasing prevalence in developing countries. The evaluation of endobronchial biopsies has emerged as a tool to differentiate between both conditions via the measurement of the reticular basement membrane (RBM) thickness with various conclusions drawn from different studies. OBJECTIVES: Compare the thickness of the RBM between asthma and COPD and evaluate other histomorphological features in both groups. DESIGN: Prospective, descriptive and analytical. SETTING: University teaching hospital. PATIENTS AND METHODS: The study included patients with COPD and irreversible and reversible asthma with diagnosis based on clinical assessment, pulmonary function tests and high-resolution computed tomography scans. Endobronchial biopsies were obtained from all patients and, using a light microscope and a computerized image analyzer, the thickness of the reticular basement membrane was calculated in all patients. We also made a qualitative assessment of other histo-morphological features. MAIN OUTCOME MEASURES: Mean RBM thickness. SAMPLE SIZE: Thirty male patients. RESULTS: The mean RBM thickness in asthmatic patients was 8.9 (2.4) micro m. The mean RBM thickness in COPD patients was 5.3 (1.1) micro m. However, there was no thickening of the RBM in patients with reversible asthma. The RBM was significantly thicker in patients with irreversible asthma than in patients with COPD or reversible asthma. There were no significant differences in epithelial desquamation or metaplasia, mucosal or submucosal inflammation, the presence of eosinophils, submucosal glandular hyperplasia or submucosal smooth muscle hyperplasia between groups. CONCLUSIONS: The thickness of the RBM is the only reproducible histopathological feature to differentiate COPD from irreversible asthma. LIMITATIONS: The study included a limited number of patients. A qualitative approach was used to compare epithelial cell injury, inflammation, submucosal glandular and muscular hyperplasia. CONFLICT OF INTEREST: None.