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Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses.

ABSTRACT: Remodeling of the peripheral airways persists during the asymptomatic phase of heaves. Assessing the histology of large bronchi could facilitate the diagnosis of heaves during remission of the disease.Airway inflammation and remodeling in endobronchial biopsy (EBB) specimens differentiate horses with heaves from controls, independently of their clinical status (exacerbation or remission).Fourteen healthy horses and 24 horses with heaves.A 14-point scoring system assessing central bronchial wall inflammation and remodeling was developed. The score was validated by 2 pathologists using specimens obtained from 18 horses (6 controls, 6 with heaves exacerbation, and 6 with heaves remission) in which lung function had been assessed with impulse oscillometry. Clinical and research application of the score was evaluated using biopsy specimens obtained from 20 additional horses (8 controls, 6 with heaves exacerbation, and 6 with heaves remission).The score was repeatable (interclass correlation coefficient = 69%). It differentiated horses with heaves in exacerbation (mean ± SD: 6.2 ± 2.2) from those in remission (4.0 ± 1.0) and controls (3.6 ± 1.7, P < 0.0001). The histological scores of horses with heaves correlated with the ratio of respiratory resistance (R) at 5 and 10 Hz (R5 : R10 ratio, r = 0.65, P = 0.03), a parameter assessing airway obstruction.The proposed histological scoring system correlates with the degree of airway obstruction measured by impulse oscillometry. However, it does not discriminate horses with heaves in remission from controls. Evaluation of EBB specimens might be considered in future research and clinical studies of respiratory diseases in horses.

SUBMITTER: Bullone M

PROVIDER: S-EPMC5032871 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses.

Bullone M M Hélie P P Joubert P P Lavoie J-P JP

Journal of veterinary internal medicine 20160816 5

<h4>Background</h4>Remodeling of the peripheral airways persists during the asymptomatic phase of heaves. Assessing the histology of large bronchi could facilitate the diagnosis of heaves during remission of the disease.<h4>Hypothesis</h4>Airway inflammation and remodeling in endobronchial biopsy (EBB) specimens differentiate horses with heaves from controls, independently of their clinical status (exacerbation or remission).<h4>Animals</h4>Fourteen healthy horses and 24 horses with heaves.<h4>M ...[more]

PMID: 27527123

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Project description:BackgroundPathological mutations in Alpha-1 Antitrypsin (AAT) protein cause retention of toxic polymers in the hepatocyte endoplasmic reticulum. The risk for cirrhosis in AAT deficiency is likely directly related to retention of these polymers within the liver. Polymers are classically identified on liver biopsy as inclusion bodies by periodic acid schiff staining after diastase treatment and immunohistochemistry. However, characterization of the polymer burden within a biopsy sample is limited to a semi-quantitative scale as described by a pathologist. Better methods to quantify polymer are needed to advance our understanding of pathogenesis of disease. Therefore, we developed a method to quantify polymer aggregation from standard histologic specimens. In addition, we sought to understand the relationship of polymer burden and other histologic findings to the presence of liver fibrosis.MethodsLiver samples from a well-categorized AATD cohort were used to develop histo-morphometric tools to measure protein aggregation.ResultsWhole-slide morphometry reliably quantifies aggregates in AATD individuals. Despite very low levels of inclusions present (0-0.41%), accumulation of globules is not linear and is associated with higher fibrosis stages. Immunohistochemistry demonstrates that fibrosis is associated with polymer accumulation and not total AAT. A proportion of patients were found to be "heavy accumulators" with a polymer burden above the upper 25% of normal distribution. Males had significantly more liver inclusions and polymer than females. These measurements also highlight interrelated phenotypes of hepatocellular degeneration and autophagy in AATD liver disease.ConclusionQuantitative inclusion analysis measures AAT accumulation in liver biopsy specimens. Quantification of polymer may identify individuals at risk for progressive disease and candidates for therapeutic interventions. Furthermore, these methods may be useful for evaluating efficacy of drugs targeting accumulation of AAT.

Dataset Information

Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses.

Publications

Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses.

Similar Datasets

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