Teng Moua

Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis

Accurate assessment of prognosis in idiopathic pulmonary fibrosis remains elusive due to significant individual radiological and physiological variability. We hypothesised that short-term radiological changes may be predictive of survival. We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Laboratory at the Mayo Clinic Rochester (Rochester, MN, USA) for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography. We assessed baseline and follow-up (time-points 1 and 2, respectively) high-resolution computed tomography scans in 55 selected idiopathic pulmonary fibrosis patients and correlated CALIPER-quantified measurements with expert radiologists’ assessments and clinical outcomes. Findings of interval change (mean 289 days) in volume of reticular densities (hazard ratio 1.91, p=0.006), total volume of interstitial abnormalities (hazard ratio 1.70, p=0.003) and per cent total interstitial abnormalities (hazard ratio 1.52, p=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short-term global interstitial lung disease progression, but not specific radiological features, was also predictive of mortality. These data demonstrate the feasibility of quantifying interval short-term changes on high-resolution computed tomography and their possible use as independent predictors of survival in idiopathic pulmonary fibrosis. Short-term quantified CT changes are predictive of survival in IPF http://ow.ly/qmbjd

Idiopathic Pulmonary Fibrosis: Evolving Concepts

Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000.

Quantitative computed tomography imaging of interstitial lung diseases.

Purpose: High-resolution chest computed tomography (HRCT) is essential in the characterization of interstitial lung disease. The HRCT features of some diseases can be diagnostic. Longitudinal monitoring with HRCT can assess progression of interstitial lung disease; however, subtle changes in the volume and character of abnormalities can be difficult to assess. Accuracy of diagnosis can be dependent on expertise and experience of the radiologist, pathologist, or clinician. Quantitative analysis of thoracic HRCT has the potential to determine the extent of disease reproducibly, classify the types of abnormalities, and automate the diagnostic process. Materials and Methods: Novel software that utilizes histogram signatures to characterize pulmonary parenchyma was used to analyze chest HRCT data, including retrospective processing of clinical CT scans and research data from the Lung Tissue Research Consortium. Additional information including physiological, pathologic, and semiquantitative radiologist assessment was available to allow comparison of quantitative results, with visual estimates of the disease, physiological parameters, and measures of disease outcome. Results: Quantitative analysis results were provided in regional volumetric quantities for statistical analysis and a graphical representation. These results suggest that quantitative HRCT analysis can serve as a biomarker with physiological, pathologic, and prognostic significance. Conclusions: It is likely that quantitative analysis of HRCT can be used in clinical practice as a means to aid in identifying a probable diagnosis, stratifying prognosis in early disease, and consistently determining progression of the disease or response to therapy. Further optimization of quantitative techniques and longitudinal analysis of well-characterized subjects would be helpful in validating these methods.

The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia

Background Recent studies have suggested that non-definitive patterns on high-resolution CT (HRCT) scan provide sufficient diagnostic specificity to forgo surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis (IPF). The objective of this study was to determine test characteristics of non-definitive HRCT patterns for identifying histopathological usual interstitial pneumonia (UIP). Methods Patients with biopsy-proven interstitial lung disease (ILD) and non-definitive HRCT scans were identified from two academic ILD centres. Test characteristics for HRCT patterns as predictors of UIP on surgical lung biopsy were derived and validated in independent cohorts. Results In the derivation cohort, 64/385 (17%) had possible UIP pattern on HRCT; 321/385 (83%) had inconsistent with UIP pattern. 113/385 (29%) patients had histopathological UIP pattern in the derivation cohort. Possible UIP pattern had a specificity of 91.2% (95% CI 87.2% to 94.3%) and a positive predictive value (PPV) of 62.5% (95% CI 49.5% to 74.3%) for UIP pattern on surgical lung biopsy. The addition of age, sex and total traction bronchiectasis score improved the PPV. Inconsistent with UIP pattern demonstrated poor PPV (22.7%, 95% CI 18.3% to 27.7%). HRCT pattern specificity was nearly identical in the validation cohort (92.7%, 95% CI 82.4% to 98.0%). The substantially higher prevalence of UIP pattern in the validation cohort improved the PPV of HRCT patterns. Conclusions A possible UIP pattern on HRCT has high specificity for UIP on surgical lung biopsy, but PPV is highly dependent on underlying prevalence. Adding clinical and radiographic features to possible UIP pattern on HRCT may provide sufficient probability of histopathological UIP across prevalence ranges to change clinical decision-making.

Characteristics and Outcomes of Small Cell Lung Cancer Patients Diagnosed During Two Lung Cancer Computed Tomographic Screening Programs in Heavy Smokers

Introduction: Small cell lung cancer (SCLC) is considered an inappropriate screening target due to its short preclinical phase and high rate of relapse despite optimal therapy. However, while intuitively screening for SCLC is inadvisable, in reality, there is a scarcity of data focusing on screen-detected SCLC and whether this intervention leads to diagnosis at an earlier clinical stage or alters outcome. Methods: We conducted a retrospective review of the baseline characteristics, treatment, and outcome of SCLC patients diagnosed during two large-scale computed tomographic screening studies conducted in heavy smokers. Results: There were 7 of 4782 and 8 of 1520 cases of SCLC identified in the Toronto and Mayo Clinic screening studies, respectively. Complete clinical data were available only for 10 subjects. The median age at diagnosis was 66 years, and 70% were female. The majority were current smokers, with a median pack-year history of 50 years. Four cases were detected on enrolment scan, four on annual computed tomography scans, and two on interim scans. Four patients had extensive disease at diagnosis. One of six limited stage patients underwent surgical resection. All 10 patients received first-line chemotherapy. Eight received radiation to at least one site. Eight patients have since died. Median survival was 11.3 months. Two patients remain disease free at 2 and 9 years, respectively. Conclusion: This study suggests that computed tomography screening is ineffective for SCLC. Efforts to reduce mortality of SCLC should instead focus on prevention through tobacco reduction programs, as well as the development of improved treatment options.

Predictors of diagnosis and survival in idiopathic pulmonary fibrosis and connective tissue disease-related usual interstitial pneumonia.

BackgroundAlthough usual interstitial pneumonia (UIP) appears to portend better survival when associated with connective tissue disease (CTD-UIP), little is known about the presenting clinical, radiologic, and pathologic features that differentiate pathologically confirmed UIP with CTD from idiopathic pulmonary fibrosis (IPF). In patients with atypical radiologic and clinical features, what specific findings predict underlying IPF vs. CTD-UIP diagnosis and their respective long term survival?MethodsA large retrospective cohort analysis was done of consecutive patients seen from 1995 through 2010 with biopsy confirmed UIP completed or reviewed at our institution. CTD-UIP was defined by independent rheumatology consultation with exclusion of all other secondary causes of lung fibrosis. Primary clinical data was collected and compared for IPF and CTD-UIP along with logistic regression performed for predictors of disease likelihood and Cox proportional hazards analysis for predictors of survival.ResultsSix hundred and twenty five patients were included in the study of which 89 had diagnosed CTD-UIP representing 7 disease entities. Survival was better among those with CTD-UIP except in UIP associated with rheumatoid arthritis, which had similar presenting features and survival to IPF. Predictors of underlying CTD included female gender, younger age, positive autoimmune serology, and inconsistent presenting radiologic findings. Only age and forced vital capacity corrected for a priori covariates were predictive of survival in CTD-UIP.ConclusionsUIP pathology occurs frequently among patients with atypically presenting clinical and radiologic features, and may represent IPF or CTD-UIP with improved prognosis if underlying CTD is diagnosed. Presenting radiologic and pathologic features alone are not predictive of underlying secondary cause or survival between the two groups.

Glycosphingolipids Mediate Pneumocystis Cell Wall β-Glucan Activation of the IL-23/IL-17 Axis in Human Dendritic Cells

Pneumocystis species are opportunistic fungal organisms that cause severe pneumonia in immune-compromised hosts, with resultant high morbidity and mortality. Recent work indicates that IL-17 responses are important components of host defense against fungal pathogens. In the present study, we demonstrate that cell-surface β-glucan components of Pneumocystis (PCBG) stimulate human dendritic cells (DCs) to secrete IL-23 and IL-6. These cytokines are well established to stimulate a T helper-17 (Th17) phenotype. Accordingly, we further observe that PCBG-stimulated human DCs interact with lymphocytes to drive the secretion of IL-17 and IL-22, both Th17-produced cytokines. The activation of DCs was shown to involve the dectin-1 receptor with a downstream activation of the Syk kinase and subsequent translocation of both the canonical and noncanonical components of the NF-κB transcription factor family. Finally, we demonstrate that glycosphingolipid-rich microdomains of the plasma membrane participate in the activation of DCs by PCBG through the accumulation of lactosylceramide at the cell surface during stimulation with PCBG. These data strongly support the idea that the β-glucan surface components of Pneumocystis drive the activation of the IL-23/IL-17 axis during this infection, through a glycosphingolipid-initiated mechanism.

Radiologic and Clinical Bronchiectasis Associated with Autosomal Dominant Polycystic Kidney Disease

Background Polycystin 1 and 2, the protein abnormalities associated with autosomal dominant polycystic kidney disease (ADPKD), are also found in airway cilia and smooth muscle cells. There is evidence of increased radiologic bronchiectasis associated with ADPKD, though the clinical and functional implications of this association are unknown. We hypothesized an increased prevalence of both radiologic and clinical bronchiectasis is associated with APDKD as compared to non-ADPKD chronic kidney disease (CKD) controls. Materials and Methods A retrospective case-control study was performed at our institution involving consecutive ADPKD and non-ADPKD chronic kidney disease (CKD) patients seen over a 13 year period with both chest CT and PFT. CTs were independently reviewed by two blinded thoracic radiologists. Manually collected clinical data included symptoms, smoker status, transplant history, and PFT findings. Results Ninety-two ADPKD and 95 non-ADPKD CKD control patients were compared. Increased prevalence of radiologic bronchiectasis, predominantly mild lower lobe disease, was found in ADPKD patients compared to CKD control (19 vs. 9%, P = 0.032, OR 2.49 (CI 1.1–5.8)). After adjustment for covariates, ADPKD was associated with increased risk of radiologic bronchiectasis (OR 2.78 (CI 1.16–7.12)). Symptomatic bronchiectasis occurred in approximately a third of ADPKD patients with radiologic disease. Smoking was associated with increased radiologic bronchiectasis in ADPKD patients (OR 3.59, CI 1.23–12.1). Conclusions Radiological bronchiectasis is increased in patients with ADPKD particularly those with smoking history as compared to non-ADPKD CKD controls. A third of such patients have symptomatic disease. Bronchiectasis should be considered in the differential in ADPKD patients with respiratory symptoms and smoking history.

Frequency and implication of autoimmune serologies in idiopathic pulmonary fibrosis.

OBJECTIVE To assess the frequency and clinical implications of positive autoimmune serologies in patients with biopsy-confirmed idiopathic pulmonary fibrosis (IPF). PATIENTS AND METHODS We reviewed the records of patients at our institution with biopsy-confirmed usual interstitial pneumonia (UIP) from January 1, 1995, through December 31, 2010, for frequency and distribution of autoimmune serologies. Patients with IPF with and without positive serologies were compared. RESULTS Three hundred eighty-nine consecutive patients with biopsy-confirmed IPF underwent serologic testing, with positive serologic test results being found in 112 (29%). Of 2051 individual screening serologic tests performed, results of 163 tests were positive (8%), with antinuclear antibody being the most frequent (47%). There was no difference in age at biopsy (P=.21), gender (P=.21), or presenting radiologic features between those with or without positive serology. More frequent use of immunosuppressive treatment (P=.02) was noted in those with positive serology. No survival difference was observed (log-rank; P=.43). Median follow-up for the whole cohort was 43.5 months. CONCLUSION Positive autoimmune serology may occur in as much as one-third of the patients with biopsy-confirmed IPF with no associated clinical implication or survival advantage. Systematic use of autoimmune laboratory panels in patients without clinical features of connective tissue disease should be reconsidered in patients with suspected UIP on chest computed tomography scan or confirmed UIP on biopsy.

Bronchoscopy assessment of acute respiratory failure in interstitial lung disease

Acute respiratory failure (ARF) in patients with interstitial lung disease (ILD) is associated with significant morbidity and mortality. Recommended assessment for acute exacerbation (AE) of ILD includes exclusion of secondary causes via fibreoptic bronchoscopy. Our aim is to assess the role of bronchoscopy during ARF‐ILD.