Deborah Assayag

Rheumatoid Arthritis–associated Interstitial Lung Disease: Radiologic Identification of Usual Interstitial Pneumonia Pattern

PURPOSE To determine the accuracy of computed tomography (CT) in identifying the histopathologic usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). MATERIALS AND METHODS All patients were enrolled into institutional review board-approved longitudinal cohorts at their respective institution, and informed consent was obtained at the time of enrollment. Images of patients with surgical lung biopsy-proved RA-ILD (n = 69) were collected from three tertiary care centers. Two experienced thoracic radiologists independently reviewed the CT scans. The CT pattern was categorized as definite UIP, possible UIP, or inconsistent with UIP in accordance with published criteria. Findings of biopsies were reviewed by an experienced lung pathologist. The sensitivity and specificity of definite CT UIP pattern to histopathologic UIP pattern were determined. The agreement between radiologists was assessed by calculating a κ score. RESULTS The histopathologic UIP pattern was present in 42 of 69 (61%) patients. Men were more likely than women to have a histopathologic UIP pattern (P = .02). Twenty patients (29%, 20 of 69) had a definite UIP pattern on CT scans. The specificity of CT UIP pattern was 96% (26 of 27; 95% confidence interval [CI]: 81%, 100%), with a negative predictive value of 53% (26 of 49). The sensitivity of CT UIP pattern was 45% (19 of 42; 95% CI: 30%, 61%), with a positive predictive value of 95% (19 of 20). The agreement between radiologists for definite UIP pattern versus not was 87% (κ = 0.67, P < .0001). CONCLUSION Definite UIP pattern on a CT scan in RA-ILD is highly specific and moderately sensitive for histopathologic UIP pattern. CT can therefore help accurately identify the UIP pattern in RA-ILD.

Predictors of Mortality and Progression in Scleroderma-Associated Interstitial Lung Disease: A Systematic Review

BACKGROUND Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc); however, prognostication of SSc-associated ILD (SSc-ILD) remains challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD. METHODS Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if they were published in English and included ≥ 10 adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies. RESULTS The initial search identified 3,145 unique citations. Twenty-seven studies, including six abstracts, met the inclusion criteria. A total of 1,616 patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc-specific variables predicted mortality and progression; however, most predictors were identified in only one study. Most studies did not fully account for potential confounders, and none of the studies included a validation cohort. Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. The extent of disease on HRCT scan was the only variable that independently predicted both mortality and ILD progression. CONCLUSIONS Mortality and ILD progression were predicted by several patient-specific, ILD-specific, and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and to identify combinations of variables that accurately predict the prognosis of SSc-ILD.

Original ResearchDiffuse Lung DiseasePredictors of Mortality and Progression in Scleroderma-Associated Interstitial Lung Disease: A Systematic Review

BACKGROUND Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc); however, prognostication of SSc-associated ILD (SSc-ILD) remains challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD. METHODS Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if they were published in English and included ≥ 10 adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies. RESULTS The initial search identified 3,145 unique citations. Twenty-seven studies, including six abstracts, met the inclusion criteria. A total of 1,616 patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc-specific variables predicted mortality and progression; however, most predictors were identified in only one study. Most studies did not fully account for potential confounders, and none of the studies included a validation cohort. Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. The extent of disease on HRCT scan was the only variable that independently predicted both mortality and ILD progression. CONCLUSIONS Mortality and ILD progression were predicted by several patient-specific, ILD-specific, and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and to identify combinations of variables that accurately predict the prognosis of SSc-ILD.

Predictors of mortality in rheumatoid arthritis-related interstitial lung disease.

Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) has a heterogeneous clinical presentation and disease course. Establishing prognosis for these patients is challenging. Identifying the factors that predict mortality in patients with RA‐ILD could help guide management. A detailed systematic review was conducted in order to identify individual variables that predict mortality in RA‐ILD. A literature review was performed using keywords and medical subject headings to identify all articles relating to the prognosis of RA‐ILD. Studies were included if they identified predictors of mortality in adults with RA‐ILD, were published in English, and included at least 10 patients with RA‐ILD. Two authors independently reviewed each citation and extracted data from all studies meeting inclusion criteria. Any differences were then resolved by consensus. A total of 10 studies met our inclusion criteria. All were observational cohort studies of variable quality. Mean age of reported patients ranged from 55 to 69 years, and 41.7% of all patients were male. Median survival ranged from 3.2 to 8.1 years. Significant predictors of mortality on multivariate analysis were older age, male gender, lower diffusion capacity for carbon monoxide, extent of fibrosis, and the presence of usual interstitial pneumonia pattern. Mortality in RA‐ILD is associated with several patient‐ and ILD‐specific variables; however, previous studies are of low quality.

Pathologic Findings and Prognosis in a Large Prospective Cohort of Chronic Hypersensitivity Pneumonitis

BACKGROUND: The ability of specific histopathologic features to predict mortality or lung transplantation in patients with chronic hypersensitivity pneumonitis (HP) is unknown. METHODS: Patients with chronic HP diagnosed by surgical lung biopsy were identified from an ongoing longitudinal cohort. The surgical lung biopsy slides were evaluated prospectively by an experienced thoracic pathologist using a standardized checklist to differentiate the major pathologic patterns and score the presence of specific histopathologic features. Cox proportional hazard analysis was used to identify independent predictors of transplant‐free survival, and Kaplan‐Meier analysis was used to visualize outcomes. RESULTS: One hundred nineteen patients were identified. Patients with a fibrotic nonspecific interstitial pneumonia (f‐NSIP) pattern, bronchiolocentric fibrosis (BF) pattern, or usual interstitial pneumonia (UIP) pattern had significantly worse transplant‐free survival than did those with a cellular NSIP (c‐NSIP) pattern or peribronchiolar inflammation with poorly formed granulomas (PI‐PFG) pattern. No survival difference among patients with an f‐NSIP pattern, a BF pattern, or a UIP pattern was found. Fibroblastic foci were identified in a subset of biopsy samples from all pathologic patterns. Peribronchiolar fibrosis was noted in all UIP cases. Independent predictors of time to death or transplantation included the presence of fibroblast foci or dense collagen fibrosis. CONCLUSIONS: Histopathologic patterns of c‐NSIP and PI‐PFG had a better transplant‐free survival than did patterns of UIP, f‐NSIP, and BF. The presence of fibroblast foci or dense collagen fibrosis correlated with progression to death or lung transplantation. Identification of fibroblast foci on biopsy samples, regardless of the underlying histopathologic pattern, may be a clinically useful predictor of survival in patients with HP.

High Resolution Computed Tomography Scoring Systems for Evaluating Interstitial Lung Disease in Systemic Sclerosis Patients

Interstitial lung disease commonly develops in patients with Systemic sclerosis (SSc). High resolution computed tomography (HRCT) has become the gold standard for detection and evaluation of lung involvement in SSc. Several HRCT scoring methods have been described and used to characterize and quantify the disease. This article reviews the different scoring systems and how they have been validated clinically and applied to prognosticate patients, assess disease progression and evaluate response to treatment.

Determining Respiratory Impairment in Connective Tissue Disease–Associated Interstitial Lung Disease

Connective tissue diseases (CTDs) can affect the lungs through diseases of the chest wall, pleura, vasculature, airways, and parenchyma. Interstitial lung disease (ILD) is a common complication of CTD associated with increased morbidity and mortality. This article describes the evaluation of respiratory impairment in patients with CTD and summarizes the evidence that guides diagnosis and management of CTD-ILD. Patients with CTD with suspected ILD should undergo clinical, physiologic, and radiologic studies to evaluate for the presence of ILD, and these results should be integrated in a multidisciplinary setting to guide diagnosis and management. Screening for ILD may also be appropriate in asymptomatic patients with high-risk features.

Evaluation of patients with fibrotic interstitial lung disease: A Canadian Thoracic Society position statement

ABSTRACT The evaluation of a patient with fibrotic interstitial lung disease (ILD) includes assessment of clinical, radiological, and often histopathological data. There are currently no specific recommendations to guide the evaluation of a patient with fibrotic ILD within the context of the Canadian practice landscape. This position statement from a multidisciplinary panel of ILD experts provides guidance related to the diagnostic modalities commonly used in the evaluation of fibrotic ILD, including radiological studies, histopathologic sampling, assessment for rheumatologic disease and need for evaluation in a multi-disciplinary setting. Key messages are provided to guide clinical practice based on a thorough review of the scientific literature.

Long-Term Azithromycin Therapy to Reduce Acute Exacerbations in Patients With Severe Chronic Obstructive Pulmonary Disease

RATIONALE According to clinical trials, azithromycin taken daily for 1 year, decreased exacerbations of chronic obstructive pulmonary disease (COPD). OBJECTIVES Effectiveness evaluation of long-term azithromycin to reduce exacerbations in severe COPD patient on optimal therapy in real-life practice. METHODS We conducted a retrospective observational study of severe COPD patients who were prescribed azithromycin (PA)(250 mg, at least 3 times weekly for at least 6 months). Comparison group included severe COPD patients not prescribed azithromycin (NPA). Data were extracted from clinical chart review. MAIN RESULTS Study included 126 PA and 69 NPA patients. They had severe airflow obstruction, mostly emphysema and one-third bronchiectasis. A predominant feature in the PA group was respiratory tract colonization with Pseudomonas aeruginosa. The mean number of exacerbations per patient per year in the PA group was 3.2 ± 2.1 before initiating azithromycin, and 2.3 ± 1.6 during following year on therapy (p < 0.001). Patients in the NPA group had 1.7 ± 1.3 and 2.5 ± 1.7 exacerbations during first and second follow-up year respectively (p < 0.001). Exacerbation changes from pre to post differed between groups (p < 0.001). Decrease in emergency visits and hospital admissions was significant in PA group. Exacerbation reductions and patient proportions having ≥2 exacerbations extended to the second year of treatment. CONCLUSION These data showed that long-term azithromycin reduces exacerbation numbers in severe COPD patients, and benefits persist beyond one year. Desirable effects are more likely to outweigh the risks and adverse events in patients colonized with Pseudomonas aeruginosa.

Comprehensive management of fibrotic interstitial lung diseases: A Canadian Thoracic Society position statement

Abstract The comprehensive management of patients with fibrotic interstitial lung disease (ILD) is multi-faceted and may include pharmacological and non-pharmacological therapies. There are no current recommendations and few resources to guide the management of patients with fibrotic ILD in Canada. This position statement provides recommendations for the management of patients with fibrotic ILD based on review of the scientific literature and consensus from a panel of ILD experts. These recommendations relate to important clinically relevant questions, and key messages are provided to guide clinical practice.