Bronchoalveolar Lavage Lymphocytes in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease

Patolia, Setu; Kakazu, Maximiliano Tamae; Chami, Hasan A.; Chua, Abigail; Diaz-Mendoza, Javier; Duggal, Abhijit; Jenkins, Alex R; Knight, Shandra L; Raghu, Ganesh; Wilson, Kevin C.

doi:10.1513/annalsats.202005-420oc

Cited by 39 publications

(27 citation statements)

References 88 publications

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“…Depending on diagnostic cut-off and study-speci c criteria for inclusion, reported frequencies of diagnostic BALL varied signi cantly but occurred less than 50% of the time in most studies, particularly when BALL was being assessed for diagnostic utility. This lower frequency suggests likely overlap with other ILD, as demonstrated by the ndings of two recent meta-analyses (4,10). Both found lower range sensitivity and speci city for BALL as a diagnostic predictor (depending on cut-off 20% vs 30%), with expected inverse relationship between sensitivity and speci city (higher speci city at the cost of lower sensitivity).…”

Section: Discussionmentioning

confidence: 91%

“…Evidence for this recommendation references prior studies demonstrating comparatively higher BAL lymphocyte counts in HP compared to other interstitial lung disease (ILD) (4)(5)(6)(7)(8)(9). Two recent systematic reviews and meta-analyses report higher BALL in HP though pooled ndings suggested less predictive characteristics (4,10). The authors highlight several important limitations including the aggregation of older studies with varied diagnostic criteria and incorporation bias, where BALL itself may have been used to make initial diagnoses for study inclusion.…”

Section: Introductionmentioning

confidence: 79%

“…A recent diagnostic guideline from the ATS/JRS/ALAT recommends the use of BALL with a lymphocyte count of greater than or equal to 30% as increasing diagnostic con dence (3). Evidence for this recommendation references prior studies demonstrating comparatively higher BAL lymphocyte counts in HP compared to other interstitial lung disease (ILD) (4)(5)(6)(7)(8)(9). Two recent systematic reviews and meta-analyses report higher BALL in HP though pooled ndings suggested less predictive characteristics (4,10).…”

Section: Introductionmentioning

confidence: 99%

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Bronchoalveolar Lavage Lymphocytosis in Hypersensitivity Pneumonitis: A Retrospective Cohort Analysis with Elimination of Incorporation Bias

Hill

Petnak

Moua

2021

Preprint

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Background: Recent studies support the diagnostic role of bronchoalveolar lavage lymphocytosis (BALL) in patients with suspected hypersensitivity pneumonitis (HP). Our study aim was to determine the spectrum of BALL findings with elimination of incorporation bias and assess correlates of positive BALL cut-off and BALL association with long-term outcomes in those with fibrotic disease (f-HP).Methods: A single-center retrospective cohort study was pursued of patients undergoing diagnostic bronchoscopy for interstitial lung disease. Strict study enrollment was based on recent ATS/JRS/ALAT diagnostic guidance meeting ‘moderate’ or higher diagnostic confidence. BALL findings were assessed in both fibrotic and non-fibrotic HP patients with regression and survival analysis pursued for correlates of positive BALL cut-off and long-term outcome. Results: A total of 148 patients (88 fibrotic and 60 non-fibrotic) meeting moderate or higher diagnostic confidence were included. Median BALL in f-HP was 15% compared to 19% in non-fibrotic patients, with only 28% of f-HP meeting diagnostic cut-off (≥ 30%) compared to 41% of non-fibrotic. For f-HP, centrilobular nodules on computed tomography was positively correlated with a diagnostic BALL (OR 4.07; p = 0.018) while honeycombing was negatively correlated (OR 6.9 x e-8; p = 0.001). Higher BALL was also associated with lower all-cause mortality (HR 0.98; p = 0.015). Conclusion: With elimination of incorporation bias, most patients with well-described HP did not meet diagnostic BALL thresholds. Higher BALL was associated with better long-term survival in those with fibrosis, but its diagnostic role may be more additive than characteristic or distinguishing.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bronchoalveolar Lavage Lymphocytosis in Hypersensitivity Pneumonitis: A Retrospective Cohort Analysis with Elimination of Incorporation Bias

Hill

Petnak

Moua

2021

Preprint

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“…Bronchoalveolar lavage (BAL) cell analysis has been advocated by some to differentiate sarcoidosis from HP on the basis of the percentage of lymphocytes or the ratio of CD4+/CD8+ lymphocytes. However, these BAL analyses have not been found to be adequately discriminatory ( 46 , 47 ).…”

Section: Occupational and Environmental Exposuresmentioning

confidence: 93%

Granulomatous Sarcoidosis Mimics

Judson¹

2021

Front. Med.

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Many granulomatous diseases can mimic sarcoidosis histologically and in terms of their clinical features. These mimics include infectious granulomatous diseases, granulomatous reactions to occupational and environmental exposures, granulomatous drug reactions, vasculitides and idiopathic granulomatous conditions. It is important to distinguish sarcoidosis from these mimics, as a misdiagnosis of these diseases may have serious consequences. This manuscript reviews numerous sarcoidosis mimics and describes features of these diseases that may allow them to be differentiated from sarcoidosis. Distinguishing features between sarcoidosis and its mimics requires a careful review of the medical history, symptoms, demographics, radiographic findings, histologic features, and additional laboratory data. Understanding the clinical characteristics of sarcoidosis and its mimics should lead to more accurate diagnoses and treatment of granulomatous disorders that should improve the care of these patients. As the diagnostic criteria of sarcoidosis are not standardized, it is possible that some of these sarcoidosis mimics may represent varied clinical presentations of sarcoidosis itself.

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“…Adderley reported that the proportion of BAL lymphocytes was 42.8% in patients with chronic hypersensitivity pneumonia (CHP) and 10.0% in IPF patients [ 5 ]. In addition, Patolia et al reported that a threshold of 20% BALF lymphocyte fraction could distinguish fibrotic HP from IPF, with sensitivity and specificity higher than 60% [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Quantitative parameters of lymphocyte nuclear morphology in bronchoalveolar lavage fluid as novel biomarkers for sarcoidosis

Horimasu

Yamaguchi

Sakamoto

et al. 2021

Orphanet J Rare Dis

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Background Bronchoalveolar lavage (BAL) is one of the fundamental examinations for the differential diagnosis of interstitial lung diseases (ILDs), and lymphocytosis strongly indicates alternative diagnoses rather than idiopathic pulmonary fibrosis. However, the BALF lymphocytosis is observed in several ILDs. We considered that quantitative evaluation of the BALF lymphocyte nuclear morphology would be useful in the differential diagnosis of ILDs with increased BALF lymphocyte fraction. Results One hundred and twenty-one patients with ILDs having increased BALF lymphocyte fraction were recruited (68 in the development cohort and 53 in the validation cohort). In the development cohort, BALF lymphocyte nuclei in sarcoidosis patients showed significantly smaller areas, shorter perimeters, lower radius ratios, and increased roundness than those of other ILD patients (p < 0.001 for each). Next, the fractions of lymphocytes with small areas, short perimeters, low radius ratios, and increased roundness, which were determined based on receiver operating characteristic (ROC) analyses-based thresholds, were demonstrated to be higher in sarcoidosis patients than in the other ILD patients (p < 0.001 for each). Furthermore, when we combined size-representing parameters with shape-representing parameters, the fraction of lymphocytes with small and round nuclei showed approximately 0.90 of area under the ROC curve in discriminating sarcoidosis both in the development cohort and the validation cohort. Conclusion This study is the first to demonstrate the usefulness of quantitative parameters of BALF lymphocyte nuclear morphology as novel biomarkers for sarcoidosis.

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Bronchoalveolar Lavage Lymphocytes in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease

Cited by 39 publications

References 88 publications

Bronchoalveolar Lavage Lymphocytosis in Hypersensitivity Pneumonitis: A Retrospective Cohort Analysis with Elimination of Incorporation Bias

Bronchoalveolar Lavage Lymphocytosis in Hypersensitivity Pneumonitis: A Retrospective Cohort Analysis with Elimination of Incorporation Bias

Granulomatous Sarcoidosis Mimics

Quantitative parameters of lymphocyte nuclear morphology in bronchoalveolar lavage fluid as novel biomarkers for sarcoidosis

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