Chest
Volume 147, Issue 2, February 2015, Pages 415-422
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Original Research: Diffuse Lung Disease
The Clinical Course of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

https://doi.org/10.1378/chest.14-0711Get rights and content

BACKGROUND

Current understanding of the clinical course of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is poor and based predominantly on small case series. In our clinical experience, we have found that the diagnosis of DIPNECH is frequently delayed because respiratory symptoms are ascribed to other lung conditions. The objectives of this study were to collect and analyze longitudinal clinical data on pulmonary physiology, chest high-resolution CT (HRCT) imaging, and therapies to better delineate the course of disease.

METHODS

We established a cohort of patients (N = 30) with DIPNECH seen at our institution. We used descriptive statistics to summarize cohort characteristics and longitudinal analytic techniques to model FEV1 % predicted (FEV1%) over time.

RESULTS

All subjects were women who presented with long-standing cough and dyspnea. The majority had an FEV1% < 50% at the time of diagnosis. Forty percent were given a diagnosis of asthma as the cause for physiologic obstruction. The mean FEV1% for the entire cohort showed no statistically significant decline over time, but 26% of the subjects experienced a 10% decline in FEV1 within 2 years. Among the pathology samples available for review, 28% (five of 18) had typical carcinoids and 44% had associated constrictive bronchiolitis. We propose clinical diagnostic criteria for DIPNECH that incorporate demographic, pulmonary physiology, HRCT imaging, and transbronchial and surgical lung biopsy data.

CONCLUSIONS

DIPNECH is a female-predominant lung disease manifested by dyspnea and cough, physiologic obstruction, and nodules on HRCT imaging. Additional research is needed to understand the natural history of this disease and validate the proposed diagnostic criteria.

Section snippets

Subjects

This study was conducted in accordance with the amended Declaration of Helsinki. This protocol was approved by the National Jewish Health (NJH) Institutional Review Board (HS#2530). Ninety-three potential subjects were identified by query of the NJH Clinical Research Database for “neuroendocrine hyperplasia” and “age ≥ 18” and “high-resolution chest CT.” Of these 93 patients, 21 could be verified as having DIPNECH by a pathology report. From June 2011 to May 2013, nine additional patients were

Results

All subjects were women. The average age at diagnosis was 62 years. Baseline characteristics are presented in Table 1. The majority of subjects (63%) never smoked, and the remaining subjects had quit smoking prior to DIPECH diagnosis. The most common symptoms were chronic cough and dyspnea. In general, cough developed first, often more than 10 years prior to diagnosis. Medical records for the time prior to receiving a DIPNECH diagnosis were available for 27 subjects. Of these, 12 had been given

Discussion

We identified 30 patients with DIPNECH followed at our institution and detailed their clinical characteristics and disease course over time. To our knowledge, this DIPNECH cohort is the largest assembled. We observed a disease that predominately affects middle-aged women with slowly progressive physiologic lung obstruction. The striking sex bias of this disease has been observed in previous reports and remains unexplained.5

We observed substantial heterogeneity in longitudinal disease behavior.

Conclusions

DIPNECH is a neuroendocrine cell proliferation that is predominately seen in middle-aged women. The diagnosis often is delayed until moderate to severe obstruction is present. This disease needs to be considered in the setting of obstructive physiology, particularly when diffuse pulmonary nodules and mosaic pattern air trapping are present on HRCT scan. Further studies are needed to improve understanding of the pathogenesis of this disease, particularly the sex bias, and to test the proposed

Acknowledgments

Author contributions: L. L. C. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. L. L. C., J. H. C., R. D. A., and Z. L. contributed to the study design, data analysis, interpretation of results, writing and revision of the manuscript, and final approval of the manuscript; J. Y. R. and K. Y. contributed to the data collection and revision and final approval of the manuscript; R. M. T. and J. A. K.

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FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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