Early versus late onset interstitial lung disease in rheumatoid arthritis: An observational study of risk factors and mortality in Ontario, Canada.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) can occur as a manifestation of rheumatoid arthritis (RA) at various times in the disease course. We aimed to identify factors associated with early versus late onset RA-ILD and how the timing of RA-ILD influenced surgical lung biopsy completion and mortality. METHODS: We performed a retrospective observational study using health services data from Ontario, Canada. We identified RA cases between 2000 and 2020 using the Ontario Rheumatoid Arthritis Database. RA-ILD diagnosis required repeat physician visits for ILD, with early RA-ILD defined as within 1 year of RA diagnosis. We performed multivariable logistic regression to identify factors associated with early RA-ILD and surgical lung biopsy completion, and multivariable cox-proportional hazards regression to evaluate the association of early versus late RA-ILD on all-cause and RA-ILD related mortality. RESULTS: In total, we identified 3717 cases of RA-ILD. Older age at RA diagnosis [OR 1.04 (95%CI 1.03-1.05), p < 0.0001], female sex [OR 1.16 (95%CI 1.01-1.35), p = 0.04] and immigrating to Ontario [OR 1.70 (95%CI 1.35-2.14), p < 0.0001] was associated with early RA-ILD. Patients with early versus late RA-ILD experienced similar odds of undergoing a surgical lung biopsy [OR 1.34 (95%CI 0.83-2.16), p = 0.23]. Early RA-ILD was associated with increased all-cause mortality [HR 1.17 (95%CI 1.07-1.29), p = 0.0009], primarily driven by an increase in RA-ILD related mortality [HR 1.45 (95%CI 1.19-1.76), p = 0.0003]. CONCLUSION: Age at RA onset, female sex and immigration status are associated with early RA-ILD. Patients with early RA-ILD experience increased all-cause and RA-ILD related mortality after adjusting for demographics and comorbidities.

Clinical implications of frailty assessed in hospitalized patients with acute-exacerbation of interstitial lung disease.

BACKGROUND: Approximately 50% of patients with interstitial lung disease (ILD) experience frailty, which remains unexplored in acute exacerbations of ILD (AE-ILD). A better understanding may help with prognostication and resource planning. We evaluated the association of frailty with clinical characteristics, physical function, hospital outcomes, and post-AE-ILD recovery. METHODS: Retrospective cohort study of AE-ILD patients (01/2015-10/2019) with frailty (proportion ≥0.25) on a 30-item cumulative-deficits index. Frail and non-frail patients were compared for pre- and post-hospitalization clinical characteristics, adjusted for age, sex, and ILD diagnosis. One-year mortality, considering transplantation as a competing risk, was analysed adjusting for age, frailty, and Charlson Comorbidity Index (CCI). RESULTS: 89 AE-ILD patients were admitted (median: 67 years, 63% idiopathic pulmonary fibrosis). 31 were frail, which was associated with older age, greater CCI, lower 6-min walk distance, and decreased independence pre-hospitalization. Frail patients had more major complications (32% vs 10%, p = .01) and required more multidisciplinary support during hospitalization. Frailty was not associated with 1-year mortality (HR: 0.97, 95%CI: [0.45-2.10]) factoring transplantation as a competing risk. CONCLUSIONS: Frailty was associated with reduced exercise capacity, increased comorbidities and hospital complications. Identifying frailty may highlight those requiring additional multidisciplinary support, but further study is needed to explore whether frailty is modifiable with AE-ILD.

Computed tomography-based body composition measures in COPD and their association with clinical outcomes: A systematic review.

BACKGROUND: Computed tomography (CT) is commonly utilized in chronic obstructive pulmonary disease (COPD) for lung cancer screening and emphysema characterization. Computed tomography-morphometric analysis of body composition (muscle mass and adiposity) has gained increased recognition as a marker of disease severity and prognosis. This systematic review aimed to describe the CT-methodology used to assess body composition and identify the association of body composition measures and disease severity, health-related quality of life (HRQL), cardiometabolic risk factors, respiratory exacerbations, and survival in patients with COPD. METHODS: Six databases were searched (inception-September 2021) for studies evaluating adult COPD patients using thoracic or abdominal CT-muscle or adiposity body composition measures. The systematic review was conducted in accordance with the PRISMA guidelines. RESULTS: Twenty eight articles were included with 15,431 COPD patients, across all GOLD stages with 77% males, age range (mean/median 59-78 years), and BMI range 19.8-29.3 kg/m2. There was heterogeneity in assessment of muscle mass and adiposity using thoracic (n = 22) and abdominal (n = 8) CT-scans, capturing different muscle groups, anatomic locations, and adiposity compartments (visceral, subcutaneous, and epicardial). Low muscle mass and increased adiposity were associated with increased COPD severity measures (lung function, exercise capacity, dyspnea) and lower HRQL, but were not consistent across studies. Increased visceral adiposity (n = 6) was associated with cardiovascular disease or risk factors (hypertension, hyperlipidemia, and diabetes). Low muscle CSA was prognostic of respiratory exacerbations or mortality in three of six studies, whereas the relationship with increased intermuscular adiposity and greater mortality was only observed in one of three studies. CONCLUSION: There was significant variability in CT-body composition measures. In several studies, low muscle mass was associated with increased disease severity and lower HRQL, whereas adiposity with cardiovascular disease/risk factors. Given the heterogeneity in body composition measures and clinical outcomes, the prognostic utility of CT-body composition in COPD requires further study.

Clinical outcomes associated with computed tomography-based body composition measures in lung transplantation: a systematic review.

Computed tomography (CT) is gaining increased recognition in the assessment of body composition in lung transplant (LTx) candidates as a prognostic marker of post-transplant outcomes. This systematic review was conducted to describe the methodology of CT measures of body composition used in LTx patients and its association with post-transplant outcomes. Six databases were searched (inception-April 2020) for studies of adult LTx patients with thoracic or abdominal CT measures [muscle cross-sectional area (CSA) and/or adiposity]. Thirteen articles were included with 1911 LTx candidates, 58% males, mean age range (48-61 years) and body mass index of 21.0-26.1 kg/m2 . Several methods were utilized using thoracic or abdominal CT scans to assess skeletal muscle (n = 11) and adiposity (n = 4) at various anatomic locations (carina, thoracic, and lumbar vertebrae), differing muscle groups, and adipose tissue compartments. Low muscle mass was associated with adverse outcomes in 6/11 studies, including longer mechanical ventilation days (n = 2), intensive care (n = 2) and hospital stay (n = 2), and mortality (n = 4). Greater subcutaneous and mediastinal fat were associated with increased risk of primary graft dysfunction (n = 2), but implications of adiposity on survival were variable across four studies. Further standardization of CT body composition assessments is needed to assess the prognostic utility of these measures on LTx outcomes.

Epidemiology and health outcomes of sarcoidosis in a universal healthcare population: a cohort study.

Sarcoidosis-related mortality appears to be rising in North America, with increasing rates in females and the elderly. We aimed to estimate trends in sarcoidosis incidence, prevalence and mortality in Ontario, Canada.We performed a cohort study using health administrative data from Ontario between 1996 and 2015. International Classification of Diseases and Ontario Health Insurance Plan codes were used for case detection. Three disease definitions were created: 1) sarcoidosis, two or more physician claims within 2 years; 2) chronic sarcoidosis, five or more physician claims within 3 years; and 3) sarcoidosis with histology, two or more physician claims with a tissue biopsy performed between claims.Overall, 18 550, 9199 and 3819 individuals with sarcoidosis, chronic sarcoidosis and sarcoidosis with histology, respectively, were identified. The prevalence of sarcoidosis was 143 per 100 000 in 2015, increasing by 116% (p<0.0001) from 1996. The increase in age-adjusted prevalence was higher in males than females (136% versus 99%; p<0.0001). The incidence of sarcoidosis declined from 7.9 to 6.8 per 100 000 between 1996 and 2014 (15% decrease; p=0.0009). A 30.3% decrease in incidence was seen among females (p<0.0001) compared with a 5.5% increase in males (p=0.47). Age- and sex-adjusted mortality rates of patients with sarcoidosis rose from 1.15% to 1.47% between 1996 and 2015 (28% increase; p=0.02), with the overall trend being nonsignificant (p=0.39). Mortality rates in patients with chronic sarcoidosis increased significantly over the study period (p=0.0008).The prevalence of sarcoidosis is rising in Ontario, with an apparent shifting trend in disease burden from females to males. Mortality is increasing in patients with chronic sarcoidosis.

Screening for Myositis Antibodies in Idiopathic Interstitial Lung Disease.

PURPOSE: International guidelines recommend screening for connective tissue disease (CTD) with autoantibodies when evaluating patients with idiopathic interstitial lung disease (ILD). Idiopathic inflammatory myositis comprises of a subgroup of CTD diagnosed with myositis antibodies (MA), often presenting with ILD. Our aim was to evaluate the utility of MA screening in patients with idiopathic ILD. METHODS: A retrospective analysis was conducted on patients referred with idiopathic ILD to a tertiary centre ILD clinic who were screened for MA. Patients with known or suspected CTD were excluded. Descriptive statistics, univariate analysis and multivariable logistic regression were used to detect associations between MA and patient characteristics. RESULTS: Of 360 patients, 165 met inclusion criteria and 44 (26.7%) were identified to have MA. Fourteen patients (8.5%) had a change in diagnosis as a result of MA screening. Multivariable logistic regression identified the presence of MA to be associated with current smoking [OR 6.87 (1.65-28.64), p = 0.008] and a diffusing capacity of < 70% predicted [OR 2.55 (1.09-5.97), p = 0.03]. In patients with a change in diagnosis due to MA screening, 3 (1.8%) underwent a surgical lung biopsy and 2 (1.2%) were previously treated with antifibrotic therapy. CONCLUSIONS: Screening for MA in patients with idiopathic ILD can contribute to a change in patient diagnosis, and may prevent invasive testing and unproven use of antifibrotic therapy. These results support the addition of MA to CTD screening panels during the initial evaluation of idiopathic ILD.

Risk of respiratory diseases among hospitalized patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a systemic disorder associated with various metabolic and inflammatory comorbidities. Although HS shares risk factors and pathogenic pathways with various respiratory conditions, few studies have explored the relationship between HS and respiratory disease. METHODS: This is a cross-sectional, case-control, population-based study that examined the United States National Inpatient Sample database from January 1, 2002, to December 31, 2012. HS was identified using ICD-9-CM codes during hospital admissions. Multivariable logistic regression was used to evaluate for adjusted associations between HS and respiratory diagnoses as compared to matched controls. RESULTS: Twenty-three thousand seven hundred and sixty-seven hospital admissions for HS were compared with 95,068 age- and sex-matched controls. HS patients had significantly higher adjusted odds of asthma (OR: 1.233; 95% CI: [1.170-1.299]; P < 0.001), chronic airway obstruction (OR: 1.532; 95% CI: [1.419-1.651]; P < 0.001), sarcoidosis (OR: 1.601; 95% CI: [1.157-2.214]; P < 0.001), and sleep apnea (OR: 1.274; 95% CI: [1.182-1.374]; P < 0.001). CONCLUSION: HS is associated with several common forms of respiratory disease. Knowledge of these associations may allow for better recognition of respiratory disease in HS patients.

A comprehensive evaluation of online inhaler use techniques for obstructive airway disease.

BACKGROUND: Pulmonary inhaler therapy is a core treatment modality for >600 million individuals affected by obstructive airways disease globally. Poor inhaler technique is associated with reduced disease control and increased health care utilization; however, many patients rely on the internet as a technical resource. This study assesses the content and quality of online resources describing inhaler techniques. METHODS: A Google search was conducted in April 2023 capturing the top 5 search results for 12 common inhaler devices. Websites were compared to product monographs for preparation/first use, inhalational technique, and post-usage/device care. They were also assessed using accepted quality metrics (GQS, DISCERN, JAMA Benchmark scores) and clinically relevant aspects based on the literature and consensus statements. RESULTS: Websites regularly excluded critical steps important for proper inhaler technique. They performed best on information related directly to inhalation technique (average median score 78%), whereas steps related to preparation/first use (58%) or post-usage/device care (50%) were less frequently addressed. Median GQS, DISCERN, and JAMA Benchmark scores were 3 [IQR 3-4], 3 [IQR 2-4], and 1 [IQR 1-3], respectively. Clinically relevant factors were only addressed in about one-fifth of websites with no websites addressing smoking cessation, environmental considerations, or risk factors for poor technique. CONCLUSIONS: This study highlights gaps in online resources describing inhaler technique, particularly related to preparation/first use and post-usage/device care steps. Clinically relevant factors were rarely addressed across websites. Improvements in these areas could lead to enhanced inhaler technique and clinical outcomes.

Rheumatoid arthritis associated interstitial lung disease: Trends in epidemiology and mortality in Ontario from 2000 to 2018.

BACKGROUND: The epidemiology and mortality of rheumatoid arthritis related interstitial lung disease (RA-ILD) have not been described in Canada. Our aim was to describe recent trends in RA-ILD prevalence, incidence, and mortality in Ontario, Canada. METHODS: This was a retrospective population-based study using repeated cross-sections from 2000 to 2018. We estimated annual age- and sex-standardized rates for RA-ILD prevalence, incidence and mortality. RESULTS: Among 184,400 RA patients identified between 2000 and 2018, 5722 (3.1%) were diagnosed with RA-ILD. Most RA-ILD patients were women (63.9%) and ≥60 years old (76.9%) at the time of RA-ILD diagnosis. RA-ILD incidence rose from 1.6 (95% confidence interval (CI) 1.3-2.0) to 3.3 (95% CI 3.0-3.6) per 1000 RA patients (204% relative increase, p < 0.0001) during this time. RA-ILD incidence increased in both sexes and all age groups over time. The cumulative prevalence of RA-ILD increased from 8.4 (95% CI 7.6-9.2) to 21.1 (95% CI 20.3-21.8) per 1000 RA patients (250% relative increase, p < 0.0001), increasing in both sexes and all age groups. All-cause and RA-ILD related mortality declined in patients with RA-ILD over time [55.1% relative reduction, (p < 0.0001) and 70.9% relative reduction, (p < 0.0001), respectively]. In RA-ILD patients, RA-ILD contributed to the cause of death in approximately 29% of cases. Men and older patients had higher all-cause and RA-ILD related mortality. CONCLUSION: In a large, diverse Canadian population, the incidence and prevalence of RA-ILD are increasing. RA-ILD related mortality is declining, but remains an important cause of death in this population.

Influence of pulmonary rehabilitation on symptoms of anxiety and depression in interstitial lung disease: A systematic review of randomized controlled trials.

BACKGROUND: Interstitial lung diseases (ILDs) cause fibrosis of lung parenchyma, leading to impaired quality of life, dyspnea, and functional decline. Individuals with ILD experience a high prevalence of anxiety and depression. Recent research has demonstrated pulmonary rehabilitation (PR) alleviates symptoms of anxiety and depression in those with COPD. RESEARCH QUESTION: What is the influence of PR on symptoms of anxiety and depression in individuals with ILD? STUDY DESIGN: We conducted a PRISMA-2020-compliant systematic review of randomized controlled trials (RCTs) investigating PR's effect on anxiety and depression in patients with ILD. We searched MEDLINE, EMBASE, Cochrane, and PsycINFO from inception until April 3, 2023. A narrative synthesis was conducted where a quantitative approach was not feasible. RESULTS: Five RCTs (n = 281) were included. Idiopathic pulmonary fibrosis (IPF) was the most common type of ILD (k = 3). One study reported clinically-significant improvements in symptoms of anxiety among patients with IPF, and two studies for symptoms of depression among patients with sarcoidosis. Dropout rates were similar between intervention and control groups. All studies were at a high risk of bias. INTERPRETATION: Pulmonary rehabilitation is not detrimental to anxiety or depression for patients with ILD, and may improve symptoms of anxiety in IPF and depression in sarcoidosis. However, no conclusion can be drawn from available evidence, which is limited by heterogeneous populations/interventions, sample sizes and unexpectedly low prevalences of clinically-significant anxiety or depression. Further adequately powered RCTs that focus on anxiety and depressive symptoms as primary outcomes are needed.

Myositis Antibodies and Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) comprises a heterogeneous group of inflammatory and fibrotic conditions, often resulting in progressive lung function decline and increased mortality. Connective tissue disease (CTD) should be considered in all patients with ILD, as distinguishing between CTD-ILD and other forms of fibrotic lung disease has important therapeutic and prognostic implications. The idiopathic inflammatory myopathies (IIM) represent a CTD subtype of growing interest to ILD experts. The expansion and availability of myositis-specific and myositis-associated antibody testing has allowed for improved disease detection and characterization. CONTENT: In this review, we highlight the relationship between myositis antibodies and ILD. Select forms of IIM, such as the antisynthetase syndrome and clinically amyopathic dermatomyositis can present with rapidly progressive ILD, warranting timely disease diagnosis and management. Disease phenotypes, prevalence, laboratory testing, prognosis, and management strategies are described according to select myositis antibodies. SUMMARY: Myositis antibodies provide valuable information for clinicians managing patients with ILD. This review aims to increase awareness of their role in disease detection, pathophysiology, and possibly therapeutics.

Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE).

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen. RESULTS: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care. CONCLUSION: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. STUDY REGISTRATION: ClinicalTrials.gov NCT04383613.

Utility of anti-neutrophil cytoplasmic antibody screening in idiopathic interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is an established manifestation of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Autoimmune serologic screening is recommended by international consensus guidelines during the evaluation of idiopathic ILD, but ANCA testing only on a case-by-case basis. OBJECTIVE: We aimed to evaluate the role of ANCA screening in patients with idiopathic ILD. METHODS: We performed a retrospective review of patients seen between September 2015 and April 2017 in the ILD clinic at Toronto General Hospital. Patients referred with confirmed or suspected connective tissue disease were excluded. Patient demographics, symptoms, chest imaging, and pulmonary function testing was collected. We performed descriptive statistics based on the presence of ANCAs and estimated operating characteristics for ANCA screening. RESULTS: In total, 360 patients with idiopathic ILD were reviewed, 159 met study inclusion criteria and 4 (2.5%) tested positive for ANCAs. Two patients (1.2%) had elevated myeloperoxidase-ANCAs (MPO-ANCA) and 2 (1.2%) had elevated proteinase-3-ANCAs (PR3-ANCA). There were no significant associations between patient demographics and ANCAs. One patient (0.6%) with PR3-ANCAs was diagnosed with vasculitis following rheumatologic evaluation. Despite negative ANCA testing, 1 patient (0.6%) was diagnosed with vasculitis following rheumatologic evaluation. The sensitivity and specificity of ANCA screening for vasculitis in patients with ILD was calculated as 50% (95% CI, 1.3%-98.7%) and 98% (95%CI, 4.4-155.5) respectively. Negative and positive likelihood ratios were 0.5 (95%CI 0.1-2.0) and 26.2 (95%CI 4.4-155.5) respectively. CONCLUSION: ANCA screening in patients with idiopathic ILD rarely yields positive results. These results support an individualized approach to ANCA testing as opposed to widespread screening.

Hospitalizations in Sarcoidosis: A Cohort Study of a Universal Healthcare Population.

Rationale: Population-based analyses of hospitalization rates from countries with universal healthcare systems are lacking for patients with sarcoidosis. Objectives: To evaluate the long-term trends in hospitalization rates and risk factors for hospitalization in patients with sarcoidosis in Ontario, Canada. Methods: We performed a cohort study using health administrative data from Ontario, Canada, between 1996 and 2015. Patients with sarcoidosis were identified by using two or more physician visits and International Classification of Diseases codes. All-cause and sarcoidosis-related hospitalization rates were age and sex standardized. Hospitalization rates between groups were analyzed by using Cochran-Armitage and Breslow-Day tests. Associations between patient characteristics and hospitalization rates were evaluated by using multivariable Poisson regression. Results: In total, 18,550 individuals with sarcoidosis experienced 33,516 all-cause and 1,725 sarcoidosis-related hospitalizations. Adjusted all-cause hospitalization rates decreased from 206.4 to 152.1 per 1,000 cases between 1996 and 2015 (26% decrease; P < 0.001). The largest decrease in all-cause hospitalization occurred in patients 18-25 years old (67% decrease; P < 0.001). Adjusted sarcoidosis-related hospitalization rates decreased from 21.8 to 4.2 per 1,000 cases between 1996 and 2015 (81% decrease; P < 0.001). The decrease in sarcoidosis-related hospitalizations was largest in women compared with men (87% vs. 72%; P = 0.004) and in those 26-35 years old (91% reduction; P < 0.001). Lower income (risk ratio, 1.27 [1.18-1.37]; P < 0.001) and rural residence (risk ratio, 1.16 [1.08-1.24]; P < 0.001) were associated with increased all-cause hospitalizations. Conclusions: Hospitalization rates in patients with sarcoidosis have decreased over the past 20 years, most substantially in patients of younger age. Important differences in the risk of hospitalization exist on the basis of sex, socioeconomic factors, and geographic factors in patients with sarcoidosis.

Ophthalmologic assessments in patients with newly diagnosed sarcoidosis: An observational study from a universal healthcare system.

INTRODUCTION: Consensus guidelines for the management of sarcoidosis recommend screening eye examinations for all patients, even in those without ocular symptoms. We aimed to determine the proportion of sarcoidosis patients that complete ophthalmologic evaluations and factors associated with their performance. METHODS: We identified patients with sarcoidosis using population health services data from Ontario, Canada between 1991 and 2019. Sarcoidosis was defined by ≥ 2 physician visits for sarcoidosis within a two-year period. Ophthalmologic evaluations were based on an optometrist or ophthalmologist visit within the year prior or two years following the diagnosis. We estimated correlations between the number of eye care professionals and proportion of sarcoidosis patients completing ophthalmologic assessments within regional health units. We evaluated for associations between ophthalmologic screening and patient characteristics using multivariable logistic regression. RESULTS: We identified 21,679 patients with sarcoidosis in Ontario. An ophthalmologic evaluation was performed in 14,751 (68.0%), with a similar number of individuals seeing ophthalmologists and optometrists (43.7% vs. 42.2%). The percentage of sarcoidosis patients undergoing an ophthalmologic evaluation within corresponding regional health units was moderately correlated with the number of practicing ophthalmologists (r = 0.64, p = 0.01), but not the number of optometrists (r = 0.08, p = 0.77). Patients who were older [OR per year 1.02 (95% CI 1.01-1.02), p < 0.001] and female [OR 1.54 (95% CI 1.44-1.63), p < 0.001] were more likely to complete ophthalmologic evaluations. Immigrants to Canada were less likely to undergo ophthalmologic assessments [OR 0.66 (95% CI 0.60-0.73), p < 0.001]. CONCLUSIONS: Most patients with sarcoidosis complete ophthalmologic examinations, though a substantial proportion does not. Young adults, men and immigrants were less likely to complete ophthalmologic evaluations. Limited access to ophthalmologists may at least in part explain why some sarcoidosis patients fail to complete ophthalmologic screening.

Practical Considerations for the Diagnosis and Treatment of Fibrotic Interstitial Lung Disease During the Coronavirus Disease 2019 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has affected virtually all aspects of patient care. Health-care systems around the world are trying simultaneously to treat patients with COVID-19, prepare for its long-term impacts, and treat patients with other acute and chronic diseases. There are multiple ways that the COVID-19 pandemic will directly affect patients with fibrotic interstitial lung disease (ILD), particularly given their common risk factors for poor outcomes. Major issues for patients with ILD will include restricted access to key components of the diagnostic process, new uncertainties in the use of common ILD pharmacotherapies, limited ability to monitor both disease severity and the presence of medication adverse effects, and significantly curtailed research activities. The purpose of this review is to summarize how COVID-19 has impacted key components of the diagnosis and management of fibrotic ILD as well as to provide strategies to mitigate these challenges. We further review major obstacles for researchers and identify priority areas for future ILD research related to COVID-19. Our goals are to provide practical considerations to support the care of patients with ILD during the COVID-19 pandemic and to provide a road map for clinicians caring for these patients during future infectious disease outbreaks.

Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of cardiomyocyte intercalated disk proteins causing sudden death. Heterozygous mutations of the desmosomal protein plakophilin-2 (PKP-2) are the commonest genetic cause of ARVC. Abnormal gap junction connexin43 expression has been reported in autosomal dominant forms of ARVC (Naxos and Carvajal disease) caused by homozygous mutations of desmosomal plakoglobin and desmoplakin. In tissue culture, suppression of PKP-2 results in decreased expression of connexin43. We sought to characterize the expression and localization of connexin43 in patients with ARVC secondary to heterozygous PKP-2 mutations. Complete PKP-2 gene sequencing of 27 ARVC patients was utilized to identify mutant genotypes. Endomyocardial biopsies of identified carriers were then assessed by immunofluorescence to visualize intercalated disk proteins. N-cadherin was targeted to highlight intercalated disks, followed by counterstaining for PKP-2 or connexin43 using confocal double immunofluorescence microscopy. Immunofluorescence was quantified using an AdobeA Photoshop protocol, and colocalization coefficients were determined. PKP-2 siRNA experiments were performed in mouse cardiomyocyte (HL1) cell culture with Western blot analysis to assess connexin43 expression following PKP-2 suppression. Missense and frameshift mutations of the PKP-2 gene were found in four patients with biopsy material available for analysis. Immunofluorescent studies showed PKP-2 localization to the intercalated disk despite mutations, but associated with decreased connexin43 expression and abnormal colocalization. PKP-2 siRNA in HL1 culture confirmed decreased connexin43 expression. Reduced connexin43 expression and localization to the intercalated disk occurs in heterozygous human PKP-2 mutations, potentially explaining the delayed conduction and propensity to develop arrhythmias seen in this disease.

Treatment of Gastroesophageal Reflux in Patients With Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Gastroesophageal reflux (GER) is common in patients with idiopathic pulmonary fibrosis (IPF) and has been proposed as a potential contributor to disease progression and exacerbation. Whether treatment of GER improves health outcomes in patients with IPF is controversial. Our objective was to review the efficacy and safety of GER treatments in IPF. METHODS: We performed a systematic review and meta-analysis, using MEDLINE, Embase, Central (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov. These databases were searched from their inception, and Google Scholar and conference abstracts were searched until September 2017 without language restrictions for randomized and observational studies evaluating the effects of pharmacologic or nonpharmacologic treatment. Primary outcomes were IPF-related mortality and all-cause mortality. Evidence was evaluated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The study was registered with PROSPERO (#CRD42017076257). RESULTS: Thirteen observational studies were identified through the search strategy, and eight were included in the meta-analysis. Pharmacologic treatment of GER was associated with a significant reduction in IPF-related mortality as compared with no GER treatment (unadjusted risk: HR, 0.60; 95% CI, 0.38-0.97; P = .04; I2 = 0%; three studies; N = 2,033; adjusted risk: HR, 0.45; 95% CI, 0.24-0.84; P = .01; I2 = 0%; three studies; N = 2,033) but not all-cause mortality (unadjusted: HR, 0.73; 95% CI, 0.45-1.2; P = .22; I2 = 46%; three studies; N = 1,316; adjusted: HR, 0.76; 95% CI, 0.31-1.84; P = .54; I2 = 89%; four studies; N = 1,585). The quality of evidence for these outcomes was low. CONCLUSIONS: Low-quality evidence suggests pharmacologic treatment of GER is associated with a reduction in IPF-related mortality but not overall mortality. Randomized trials of antacid therapy in IPF are needed.