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.

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.

Development of video animations to encourage patient-driven deprescribing: A Team Alice Study.

OBJECTIVE: Patient-driven deprescribing initiatives aim to increase patient knowledge and strengthen self-advocacy skills. This article describes the development of three animated videos designed to educate older adults about unsafe prescribing and medication harm, based on the actionable lessons from the death, by polypharmacy, of an older adult in our community. METHODS: Using a community based participatory research approach (CBPR), members of three senior centers (n = 53) and the Deprescribing Partnership of Western New York (n = 30) were recruited and participated in two rounds of focus groups to guide the video development. RESULTS: Stakeholder input led to changes in content, wording, and visual presentation. The final versions of the videos emphasize the following messages (1) "New medications and what you should know about the risks", (2) "What you should do when a doctor tells you never to take a certain medication", (3) "What you should know about medications when you are in the hospital." CONCLUSION: The study highlights the successful process of using CBPR to develop a series of videos designed to provide information on the risks of polypharmacy, and empower older adults to advocate for themselves. PRACTICE IMPLICATIONS: Animated educational videos are a novel strategy to address medication harm in older adults. This research is a critical first step to increasing patient-led discussions that reduce the incidence of medication harm and inappropriate medication use among older adults.

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.

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 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.

Clinical features of sarcoidosis associated pulmonary hypertension: Results of a multi-national registry.

BACKGROUND: Pulmonary hypertension (PH) is a significant cause of morbidity and mortality in sarcoidosis. We established a multi-national registry of sarcoidosis associated PH (SAPH) patients. METHODS: Sarcoidosis patients with PH confirmed by right heart catheterization (RHC) were studied. Patients with pulmonary artery wedge pressure (PAWP) of 15 mmHg or less and a mean pulmonary artery pressure (mPAP) ≥ 25 Hg were subsequently analyzed. Data collected included hemodynamics, forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), chest x-ray, and 6-min walk distance (6MWD). RESULTS: A total of 176 patients were analyzed. This included 84 (48%) cases identified within a year of entry into the registry and 94 (53%) with moderate to severe PH. There was a significant correlation between DLCO percent predicted (% pred) andmPAP (Rho = -0.228, p = 0.0068) and pulmonary vascular resistance (PVR) (Rho = -0.362, p < 0.0001). PVR was significantly higher in stage 4 disease than in stage 0 or 1 disease (p < 0.05 for both comparisons). About two-thirds of the SAPH patients came from the United States (US). There was a significant difference in the rate of treatment between US (67.5%) versus non-US (86%) (Chi Square 11.26, p = 0.0008) sites. CONCLUSIONS: The clinical features of SAPH were similar across multiple centers in the US, Europe, and the Middle East. The severity of SAPH was related to reduced DLCO. There were treatment differences between the US and non-US centers.

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.

Autoimmune symptoms in idiopathic pulmonary fibrosis: clinical significance.

BACKGROUND AND AIMS: Information regarding autoimmune symptoms that do not meet the diagnostic criteria for connective tissue disease in patients with idiopathic pulmonary fibrosis (IPF) is limited. The aim of the present study was to investigate differences in the clinical characteristics and prognosis of IPF patients with and without autoimmune symptoms. METHODS: Consecutive patients diagnosed with IPF (N = 96) from January 2008 to December 2012 were included. We compared the clinical characteristics of patients with and without autoimmune symptoms. Survival was compared by log-rank and Cox proportional hazard analyses. RESULTS: Thirty-six (38%) patients reported autoimmune symptoms. There were no significant differences in clinical characteristics between those with and without autoimmune symptoms. Patients with autoimmune symptoms had a better survival rate than those without symptoms [hazard ratio (HR) 0.27; 95% confidence interval (CI) 0.09-0.82; P = 0.020]. After adjusting for age, gender and smoking status, the presence of autoimmune symptoms was associated with improved survival (HR 0.29, 95% CI 0.09-0.89; P = 0.032). However, after adjusting for other covariates, including per cent predicted forced vital capacity and high-resolution computed tomography total extent score, the presence of autoimmune symptoms did not influence survival (HR 0.49, 95% CI 0.15-1.61; P = 0.240). The median follow-up period for the studied cohort was 31.5 months. CONCLUSION: It appears that autoimmune symptoms are associated with better prognosis among IPF patients. However, future studies are needed to validate our findings.

Pulmonary manifestations of systemic lupus erythematosus patients with and without antiphospholipid syndrome.

OBJECTIVE: To uncover the pulmonary manifestations of Systemic Lupus Erythematosus (SLE) patients alone and to compare findings with antiphospholipid syndrome (APS) associated with SLE. METHODS: This cross sectional comparative study was carried out at King Khalid University Hospital (KKUH)/King Saud University (KSU), a tertiary care hospital, Riyadh, Kingdom of Saudi Arabia. From June 2012 to March 2014, 96 diagnosed SLE patients with respiratory symptoms were included in the study and divided into two groups. Group one included SLE without antiphospholipid syndrome (APS) and group two SLE with APS. We compared Demographic features, clinical manifestations and findings of chest X-Ray, Arterial Blood Gases, Pulmonary function tests, six minute walk test, ventilation perfusion scan, echocardiography and chest high resolution computed tomography. RESULTS: Demographic and clinical characteristics of two groups were similar. Previous history of deep venous thrombosis (3% vs 27.6%, p=0.001), pulmonary embolism (3% vs34.5%, p<0.0001) and abortions (7.5% vs 27.6%, p=0.019) were significantly more in group two. Levels of Anticardiolipin antibody (0% vs 100%, p<0.0001) and lupus anticoagulant (1.5% vs 79.3%, p<0.0001) were also significantly higher in group two. Hypoxemia measured by pulse oximetry (43.3% vs 65.5% p=0.045, pulmonary Arterial Hypertension (15.5% vs 39.3% p=0.014)), and pulmonary embolism (3.4% vs 21.4% p=0.013) and ventilation perfusion mismatch on V/Q scan (1.5% vs 24.1% p=0.001) were more frequent in group two. CONCLUSION: Hypoxemia, pulmonary embolism and pulmonary arterial hypertension were significantly high in SLE patients with APS, requiring long term anticoagulation and treatment and close follow-up.

Pulmonary hypertension in end-stage renal disease and post renal transplantation patients.

BACKGROUND: Information regarding lung function parameters and functional capacity in renal failure and post renal transplantation patients with pulmonary hypertension (PH) is limited. The purpose of this study was to examine the clinical characteristics of patients with PH who were receiving hemodialysis (HD) or peritoneal dialysis (PD) or who had undergone renal transplantation. METHODS: A prospective study was performed on 116 patients (HD =55, PD =17, and post renal transplantation =44) who underwent Doppler echocardiography. PH was defined as systolic pulmonary artery pressure (SPAP) ≥40 mmHg. Demographic information, clinical characteristics, pulmonary function tests (PFTs) and the six-minute walk test (6MWT) were collected and compared between the patients with and without PH. RESULTS: Twelve (21.8%) patients receiving HD, four (23.5%) patients receiving PD, and eight (18.2%) post renal transplantation patients had PH. In the HD group, the physiological indicators (including pulmonary function test parameters, the final Borg score, and walking distance during the 6MWT) were all significantly lower in the patients with PH compared with those without PH (all P<0.0001). However, in the PD and post renal transplantation groups, no significant differences were noted in the demographic characteristics or in the physiological parameters when the PH patients were compared with those without PH (all P>0.05). CONCLUSIONS: Among HD patients, marked aberrations in PFT results or walking distance may identify a subset of patients suffering from PH.

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.

Pulmonary hypertension in Saudi Arabia: A single center experience.

CONTEXT: Several international studies have described the epidemiology of pulmonary hypertension (PH). However, information about the incidence and prevalence of PH in Saudi Arabia is unknown. AIMS: To report cases of PH and compare the demographic and clinical characteristics of PH due to various causes in a Saudi population. METHODS: Newly diagnosed cases of PH [defined as mean pulmonary artery pressure >25 mmHg at right heart cauterization (RHC)] were prospectively collected at a single tertiary care hospital from January 2009 and June 2012. Detailed demographic and clinical data were collected at the time of diagnosis, along with hemodynamic parameters. RESULTS: Of the total 264 patients who underwent RHC, 112 were identified as having PH. The mean age at diagnosis was 55.8 ± 15.8 years, and there was a female preponderance of 72.3%. About 88 (78.6%) of the PH patients were native Saudis and 24 (21.4%) had other origins. Twelve PH patients (10.7%) were classified in group 1 (pulmonary arterial hypertension), 7 (6.2%) in group 2 (PH due to left heart disease), 73 (65.2%) in group 3 (PH due to lung disease), 4 (3.6%) in group 4 (chronic thromboembolic PH), and 16 (14.3%) in group 5 (PH due to multifactorial mechanisms). PH associated with diastolic dysfunction was noted in 28.6% of group 2 patients, 31.5% of group 3 patients, and 25% of group 5 patients. CONCLUSIONS: These results offer the first report of incident cases of PH across five groups in Saudi Arabia.