Significance of bronchiolocentric fibrosis in patients with histopathological usual interstitial pneumonia

AimsTo evaluate the clinical significance of bronchiolocentric fibrosis (BCF) in patients with a histopathological pattern of usual interstitial pneumonia (UIP).Methods and resultsTwo hundred and fifty-two patients with pathological UIP pattern were identified. Two hundred and fifteen of these patients (215 of 252) had the multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Prospectively defined clinical, radiological and pathological features (including BCF) were recorded, and peripheral blood MUC5B genotype and telomere length were measured. BCF was observed in 38% (96 of 252) of all patients and 33% (72 of 215) of IPF patients; its presence was associated with a non-IPF diagnosis on multivariate analysis (odds ratio = 3.71, 95% confidence interval = 1.68-8.19). BCF was not significantly associated with environmental exposures, gastroesophageal reflux, cigarette smoking or radiological patterns. There was no significant association of BCF with MUC5B genotype or telomere length. BCF has no significant impact on survival time.ConclusionsMost patients with BCF and a histopathological pattern of UIP have IPF. However, this combined fibrotic pattern is associated with a non-IPF multidisciplinary diagnosis, with approximately one-quarter of these patients being diagnosed as chronic hypersensitivity pneumonia or unclassifiable interstitial fibrosis. The presence of BCF in these patients is not significantly associated with presumed clinical risk factors for bronchiolocentric involvement, radiological findings, MUC5B genotype, telomere length or survival time

To participate or not to participate? Voice and explanation effects on performance in a multi-period budget setting

Under what circumstances does giving a voice and explanation to a manager in a budget allocation setting improve their performance? The research into whether or not managers should participate or have a voice in setting their budget allocation show conflicting results on performance. This seems largely as a result of the variables being measured in importantly different ways. Whether or not the voice influences the final budget allocation and whether the budget is perceived as unfair, unfavourable or unattainable needs to be clearly articulated in the research design. This study demonstrates that the circumstances in which voice and explanation improve performance depend on whether or not the budget allocation is perceived as unfair. To date, it has been accepted practice that managers should participate in the budget setting process. However, it may be better to set a budget and explain its rationale. Over multiple budget periods care should be taken with the type of explanation given, because simply repeating last year's reason will discourage higher performance

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

BackgroundRecent 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).MethodsPatients 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.ResultsIn 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.ConclusionsA 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

Molecular markers of telomere dysfunction and senescence are common findings in the usual interstitial pneumonia pattern of lung fibrosis.

AimsIdiopathic pulmonary fibrosis (IPF) is a genetically mediated, age-associated, progressive form of pulmonary fibrosis characterised pathologically by a usual interstitial pneumonia (UIP) pattern of fibrosis. The UIP pattern is also found in pulmonary fibrosis attributable to clinical diagnoses other than IPF (non-IPF UIP), whose clinical course is similarly poor, suggesting common molecular drivers. This study investigates whether IPF and non-IPF UIP lungs similarly express markers of telomere dysfunction and senescence.Methods and resultsTo test whether patients with IPF and non-IPF UIP share molecular drivers, lung tissues from 169 IPF patients and 57 non-IPF UIP patients were histopathologically and molecularly compared. Histopathological changes in both IPF and non-IPF UIP patients included temporal heterogeneity, microscopic honeycombing, fibroblast foci, and dense collagen fibrosis. Non-IPF UIP lungs were more likely to have lymphocytic infiltration, non-caseating granulomas, airway-centred inflammation, or small airways disease. Telomeres were shorter in alveolar type II (AECII) cells of both IPF and non-IPF UIP lungs than in those of age-similar, unused donor, controls. Levels of molecular markers of senescence (p16 and p21) were elevated in lysates of IPF and non-IPF UIP lungs. Immunostaining localised expression of these proteins to AECII cells. The mucin 5B (MUC5B) gene promoter variant minor allele frequency was similar between IPF and non-IPF UIP patients, and MUC5B expression was similar in IPF and non-IPF UIP lungs.ConclusionsMolecular markers of telomere dysfunction and senescence are pathologically expressed in both IPF and non-IPF UIP lungs. These findings suggest that common molecular drivers may contribute to the pathogenesis of UIP-associated pulmonary fibrosis, regardless of the clinical diagnosis