CT Scan Findings of Probable Usual Interstitial Pneumonitis Have a High Predictive Value for Histologic Usual Interstitial Pneumonitis

doi:10.1378/chest.14-0976

Chest

Volume 147, Issue 2, February 2015, Pages 450-459

https://doi.org/10.1378/chest.14-0976 Get rights and content

The current usual interstitial pneumonitis (UIP)/idiopathic pulmonary fibrosis CT scan classification system excludes probable UIP as a diagnostic category. We sought to determine the predictive effect of probable UIP on CT scan on histology and the effect of the promoter polymorphism in MUC5B (rs35705950) on histologic and CT scan UIP diagnosis.

METHODS

The cohort included 201 subjects with pulmonary fibrosis who had lung tissue samples obtained within 1 year of chest CT scan. UIP diagnosis on CT scan was categorized as inconsistent with, indeterminate, probable, or definite UIP by two to three pulmonary radiologists. Tissue slides were scored by two expert pulmonary pathologists. All subjects with available DNA (N = 200) were genotyped for rs35705950.

RESULTS

The proportion of CT scan diagnoses were as follows: inconsistent with (69 of 201, 34.3%), indeterminate (72 of 201, 35.8%), probable (34 of 201, 16.9%), and definite (26 of 201, 12.9%) UIP. Subjects with probable UIP on CT scan were more likely to have histologic probable/definite UIP than subjects with indeterminate UIP on CT scan (82.4% [28 of 34] vs 54.2% [39 of 72]; P = .01). CT scan and microscopic honeycombing were not associated with each other (P = .76). The minor (T) allele of the MUC5B polymorphism was associated with concordant CT scan and histologic UIP diagnosis (P = .03).

CONCLUSIONS

Probable UIP on CT scan is associated with a higher rate of histologic UIP than indeterminate UIP on CT scan suggesting that they are distinct groups and should not be combined into a single CT scan category as currently recommended by guidelines. CT scan and microscopic honeycombing may be dissimilar entities. The T allele at rs35705950 predicts a UIP diagnosis by both chest CT scan and histology.

Section snippets

Materials and Methods

This Health Insurance Portability and Accountability Act (HIPAA) compliant study was approved by our institutional review board (NJH 1441A). This study was conducted in accordance with the amended Declaration of Helsinki. Consent was obtained from all subjects.

Results

The cohort demographics are summarized in Table 1. Average age was 62.9 years ! 10.2 years. Men comprised 62% of the cohort (125 of 201). Approximately 61% of subjects were former or current smokers. The distribution of genotype at the genetic locus rs35705950 did not deviate significantly from the expected Hardy-Weinberg equilibrium (P = .08): GG 98 (49%), GT 91 (46%), and TT 11 (6%).⁵

There was fair to moderate agreement between readers for CT scan findings (Table 2). The CT scan findings as

Discussion

Our study showed that a histologic UIP diagnosis was more often present in subjects with probable UIP on CT scan than indeterminate UIP on CT scan. Our data also show that there is no agreement or association between CT scan honeycombing and microscopic honeycombing, implying that they may represent different structures in the fibrotic lung. Finally, our study also showed that the T allele is associated with a concordant UIP diagnosis on chest CT scan and histology.

Prior studies have indicated

Conclusions

The significant difference between the histology of indeterminate UIP on chest CT scan and probable UIP on chest CT scan suggests that current guidelines (which combine these two groups into the possible UIP category) should separate these groups. Those with probable UIP on CT scan very often have UIP on histology. CT scan and histologic honeycombing are not associated, which implies that they may not be identical entities, though more study is necessary in this regard. The T allele of the

Acknowledgments

Author contributions: J. H. C. had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. J. H. C., A. L. P., and D. A. L. contributed to study design; J. L. T. contributed by coordinating the clinical evaluations; J. H. C., A. C., C. D. C., and S. D. G. contributed to radiologic and pathologic phenotyping of study subjects; D. F. M. contributed by managing the database; A. L. P. and T. E. F. contributed to data

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: This article was presented at the Radiological Society of North America Annual Meeting, December 4, 2013, Chicago, IL. FUNDING/SUPPORT: The research presented here was supported by the following grants: National Institutes of Health (NIH) R01 HL097163 (Dr D. A. Schwartz), VA-Merit 1I01BX001534 (Dr D. A. Schwartz), NIH P01 HL092870 (Dr D. A. Schwartz), and NIH R01 HL095393 (Dr D. A. Schwartz). Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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Chest

Original Research:Diffuse Lung DiseaseCT Scan Findings of Probable Usual Interstitial Pneumonitis Have a High Predictive Value for Histologic Usual Interstitial Pneumonitis

METHODS

RESULTS

CONCLUSIONS

Section snippets

Materials and Methods

Results

Discussion

Conclusions

Acknowledgments

Am J Hum Genet

Chest

Pathol Res Pract

Eur J Radiol

Chest

Clinical and pathologic features of familial interstitial pneumonia

Am J Respir Crit Care Med

A mutation in the surfactant protein C gene associated with familial interstitial lung disease

N Engl J Med

Telomerase mutations in families with idiopathic pulmonary fibrosis

N Engl J Med

A common MUC5B promoter polymorphism and pulmonary fibrosis

N Engl J Med

The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population

PLoS ONE

Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis

JAMA

Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis

Thorax

Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis

Nat Genet

A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis

N Engl J Med

Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis

Thorax

Nonspecific interstitial pneumonia: correlation between thin-section CT findings and pathologic subgroups in 55 patients

Radiology

Hermansky-Pudlak syndrome with diffuse pulmonary fibrosis: radiologic-pathologic correlation

J Comput Assist Tomogr

Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring

AJR Am J Roentgenol

Usual interstitial pneumonia: histologic correlation with high-resolution CT

Radiology

Original Research:Diffuse Lung Disease
CT Scan Findings of Probable Usual Interstitial Pneumonitis Have a High Predictive Value for Histologic Usual Interstitial Pneumonitis