A Clinical Decision Tool for Risk Stratifying Patients with Systemic Sclerosis-Related Pulmonary Hypertension.

We devised a scoring system to identify patients with systemic sclerosis (SSc) at risk for pulmonary hypertension (PH) and predict all-cause mortality. Using 7 variables obtained via pulmonary function testing, echocardiography, and computed tomographic chest imaging, we applied the score to a retrospective cohort of 117 patients with SSc. There were 60 (51.3%) who were diagnosed with PH by right heart catheterization. Using a scoring threshold ≥ 0, our decision tool predicted PH with a sensitivity, specificity, and accuracy of 0.87 (95% CI 0.75, 0.94), 0.74 (95% CI 0.60, 0.84), and 0.80 (95% CI 0.72, 0.87), respectively. When adjusted for age at PH diagnosis, sex, and receipt of pulmonary arterial vasodilators, each one-point score increase was associated with an adjusted HR of 1.19 (95% CI 1.05, 1.34) for all-cause mortality. With further validation in external cohorts, our simplified clinical decision tool may better streamline earlier detection of PH in SSc.

A Multimodal Prediction Model for Diagnosing Pulmonary Hypertension in Systemic Sclerosis.

OBJECTIVE: Diagnosis of pulmonary hypertension (PH) in systemic sclerosis (SSc) requires an invasive right heart catheterization (RHC), often based on an elevated estimated pulmonary artery systolic pressure on screening echocardiography. However, because of the poor specificity of echocardiography, a greater number of patients undergo RHC than necessary, exposing patients to potentially avoidable complication risks. The development of improved prediction models for PH in SSc may inform decision-making for RHC in these patients. METHODS: We conducted a retrospective study of 130 patients with SSc; 66 (50.8%) were diagnosed with PH by RHC. We used data from pulmonary function testing, electrocardiography, echocardiography, and computed tomography to identify and compare the performance characteristics of 3 models predicting the presence of PH: 1) random forest, 2) classification and regression tree, and 3) logistic regression. For each model, we generated receiver operating curves and calculated sensitivity and specificity. We internally validated models using a train-test split of the data. RESULTS: The random forest model performed best with an area under the curve of 0.92 (95% confidence interval [95% CI] 0.83-1.00), sensitivity of 0.95 (95% CI 0.75-1.00), and specificity of 0.80 (95% CI 0.56-0.94). The 2 most important variables in our random forest model were pulmonary artery diameter on chest computed tomography and diffusing capacity for carbon monoxide on pulmonary function testing. CONCLUSIONS: In patients with SSc, a random forest model can aid in the detection of PH with high sensitivity and specificity and may allow for better patient selection for RHC, thereby minimizing patient risk.

Tumour Genome Characterization of a Rare Case of Pulmonary Enteric Adenocarcinoma and Prior Colon Adenocarcinoma.

Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of lung adenocarcinoma first described in the early 1990s in a lung tumour with overlapping lung and small intestine features. It is a rare tumour with fewer than 300 cases described in the published literature and was only formally classified in 2011. Given these characteristics the diagnosis is challenging, but even more so in a patient with prior gastrointestinal malignancy. A 68-year-old Caucasian female presented with a cough and was found to have a right upper lobe mass. Her history was significant for a pT3N1 colon adenocarcinoma. The resected lung tumour showed invasive lung adenocarcinoma but also features of colorectal origin. Immuno-stains were strongly and diffusely positive for lung and enteric markers. Multi-region, whole-exome sequencing of the mass and archival tissue from the prior colorectal cancer showed distinct genomic signatures with higher mutational burden in the PEAC and very minimal overlap in mutations between the two tumours. This case highlights the challenge of diagnosing rare lung tumours, but more specifically PEAC in a patient with prior gastro-intestinal cancer. Our use of multi-region, next-generation sequencing revealed distinct genomic signatures between the two tumours further supporting our diagnosis, and evidence of PEAC intra-tumour heterogeneity.

Eosinophilic Granulomatosis With Polyangiitis: Clinical Predictors of Long-term Asthma Severity.

BACKGROUND: The long-term clinical course of asthma in patients with eosinophilic granulomatosis with polyangiitis (EGPA) remains unclear. We aimed to characterize long-term asthma in EGPA and to identify baseline predictors of long-term asthma severity. METHODS: This retrospective cohort study included patients who fulfilled standardized criteria for EGPA who were followed up in a single referral center between 1990 and 2017. Baseline and 3 (± 1) years of follow-up clinical, laboratory, and pulmonary function data were analyzed. RESULTS: Eighty-nine patients with EGPA and a documented asthma assessment at baseline and at 3 years from diagnosis were included. Severe/uncontrolled asthma was observed in 42.7% of patients at diagnosis and was associated with previous history of respiratory allergy (P < .01), elevated serum total IgE levels (P < .05), and increased use of high-dose inhaled corticosteroids (ICSs; P < .05) and oral corticosteroids (OCSs; P < .001) for respiratory symptoms the year before the EGPA diagnosis. During follow-up, an improvement or worsening in asthma severity was noted in 12.3% and 10.1% of patients, respectively. Severe/uncontrolled asthma was present in 40.5% of patients at 3 years and was associated with increased airway resistance on pulmonary function tests (PFTs; P < .05). Long-term PFTs did not improve during long-term follow-up regardless of ICS or OCS therapy. Multivariate binary logistic regression results indicated that severe rhinosinusitis (P = .038), pulmonary infiltrates (P = .011), overweight (BMI ≥ 25 kg/m2; P = .041), and severe/uncontrolled asthma at vasculitis diagnosis (P < .001) independently predicted severe/uncontrolled asthma at the 3-year end point. CONCLUSIONS: In patients with asthma with EGPA, long-term severe/uncontrolled asthma is associated with baseline pulmonary and ear, nose, and throat manifestations but not with clear-cut vasculitic features.

Severe/uncontrolled asthma and overall survival in atopic patients with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Although asthma, rhinitis/rhinosinusitis and peripheral eosinophilia are present in virtually all patients with eosinophilic granulomatosis with polyangiitis (EGPA), the role of atopy in these patients is not well defined. OBJECTIVE: To clarify the role of atopy in patients affected with EGPA. METHODS: Clinical, laboratory and standard spirometry data have been abstracted from medical records. Only patients who underwent skin and/or specific IgE testing for common aeroallergens before the vasculitic phase were included. RESULTS: Overall, 33.5% (63) of our patients underwent skin and/or specific IgE testing to aeroallergens. Atopy related to aeroallergens was confirmed in 22.3% (two-third of those tested), and was associated with more severe/uncontrolled asthma (p < 0.001), including a greater use of oral glucocorticoids for respiratory manifestations the year before the diagnosis of EGPA (p = 0.013). Atopic patients with EGPA had higher total serum IgE levels and less renal disease at EGPA diagnosis compared to non-atopic patients (p < 0.05). Among atopic patients, the majority had multiple sensitizations (76%); dust mite and grass pollen were the most common respiratory allergens identified. The number of allergens did not correlate with peripheral eosinophilia, total serum IgE, ESR, or measures of airway obstruction (p > 0.05 in all cases). The presence of atopy increased the risk of severe/uncontrolled asthma, but not the risk of severe vasculitis (Five Factor Score≥1). Atopic patients had a better overall survival (p = 0.027). CONCLUSION: In EGPA, atopy is associated with better prognosis and more severe/uncontrolled asthma manifestations in the year before the development of vasculitis, but not with more severe vasculitis at presentation.

Brief Report on the Detection of the EGFR T790M Mutation in Exhaled Breath Condensate from Lung Cancer Patients.

The EGFR T790M somatic mutation is the most common mechanism of resistance to tyrosine kinase inhibitors in NSCLC. Patients with advanced disease are not always amenable to repeat biopsy for further molecular analysis. Developing noninvasive methods to detect T790M in cell-free DNA in the absence of tissue is being actively investigated. Unfortunately, the low sensitivity of plasma for detection of T790M has limited its clinical use. Exhaled breath condensate (EBC) is an easily collected sample that is known to harbor cell-free DNA, including lung cancer mutations. This report details the potential utility of exhaled breath condensate in the detection of the EGFR T790M mutation.

Pulmonary blastoma: a case report and review of the literature.

BACKGROUND: Pulmonary blastomas are a rare aggressive neoplasm comprising 0.25-0.5% of all primary lung tumors and portend a poor prognosis. They display a biphasic histology with mesenchymal and epithelial components. Historically, the term pulmonary blastoma had included both pure fetal adenocarcinomas, pleuropulmonary blastomas as well as the classic biphasic blastomas. However recent World Health Organisation re-classifications separated well-differentiated fetal adenocarcinomas and pleuropulmonary blastomas from the biphasic tumours. CASE PRESENTATION: We present a case of a systemically well 67-year-old Caucasian male who presented with haemoptysis. Investigations confirmed the presence of a large right-sided lung mass and biopsy identified non-small cell carcinoma. The resected tumour was markedly necrotic revealing a biphasic pattern. It was composed of malignant glandular tissue with sub-nuclear vacuoles, associated with a pleomorphic stromal malignant blastematous component, characteristic of classic biphasic pulmonary blastoma. CONCLUSION: We present a case of a classic biphasic pulmonary blastoma, a rare lung cancer occurring at an earlier age and portending to poorer prognosis than other more common lung cancers. Given the small number of cases and recent re-classification, interpreting the published epidemiology and clinical features of this disease is difficult. Many earlier reports may have included fetal adenocarcinomas (in particular high grade variant), which need to be considered when discussing treatment and prognosis with newly-diagnosed patients. Much could be gained from a central registry of individual experiences to improve our understanding of this rare lung cancer.