The Role of Neutrophils in the Pathogenesis of Idiopathic Pulmonary Fibrosis

doi:10.1378/chest.112.5.1338

Chest

Volume 112, Issue 5, November 1997, Pages 1338-1343

https://doi.org/10.1378/chest.112.5.1338 Get rights and content

Study objectives

The prognostic value of the neutrophil count in BAL fluid (BALF) has been controversial. The role of neutrophils in this inflammatory lung disease, therefore, was evaluated in this study by additional measures.

Materials and methods

We performed BAL in 22 patients with idiopathic pulmonary fibrosis (IPF) diagnosed by open lung biopsy specimen. Percent polymorphonuclear leukocyte (PMN) in BALF and absolute neutrophil counts were compared with those of normal nonsmokers. Elastase complexed to alpha-1-proteinase inhibitor (α₁-PI) in plasma and BALF was measured as a marker of elastase burden, and neutrophil distribution in 22 lung tissues was observed by immunohistochemistry using antineutrophil elastase antibody.

Results

Percent PMN and absolute neutrophil counts in BALF did not increase in patients with IPF as compared with normal nonsmokers (n=I5); the plasma elastase-α₁-PI complex value (mean±SE) of patients with IPF (668.5±112.4 ng/mL) was significantly high as compared with that of normal nonsmokers (130.3±21.3, p>0.001). In addition, the BALF elastase-α₁-PI complex value (mean±SE) of patients with IPF was also significantly high (333.1 ±87.0 ng/mg albumin) as compared with that of normal nonsmokers (83.1 ±29.3 ng/mg albumin, p>0.05). Immunohistochemistry demonstrated considerable numbers of neutrophils infiltrating the lung parenchyma in biopsy specimens obtained by open lung biopsy.

Conclusions

These results suggested that although the neutrophil count in BALF could not represent the distribution of neutrophil in the lung, high levels of neutrophil elastase were demonstrated in lung parenchyma and also in both BALF and sera. Therefore, neutrophils might indeed play an important role in the pathogenesis of IPF.

Section snippets

Subjects

The protocols of this study were approved by the institutional review board for human studies, and informed written consent was obtained from the subjects.

A diagnosis of IPF required the following:¹²,¹³ (1) no clinical history of exposure to environmental agents known to cause interstitial lung disease, no history suggestive of extrinsic allergic alveolitis, and no history of chronic lung infection or left ventricular failure; (2) evidence of interstitial infiltrates on chest radiograph or

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: Reprint requests: Jiro Fujita, MD, First Department of Internal Medicine, Kagawa Medical School, 1750-1, Miki-cho, Kita-gun, Kagawa, 761-07, Japan

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Chest

Laboratory and Animal InvestigationsThe Role of Neutrophils in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Study objectives

Materials and methods

Results

Conclusions

Section snippets

Subjects

Chest

Hum Pathol

Chest

Interstitial lung diseases of unknown cause: disorders characterized by chronic inflammation of the lower respiratory tract

N Engl J Med

Idiopathic pulmonary fibrosis

Bronchoalveolar lavage fluid and venous blood constituents in idiopathic pulmonary fibrosis and selected comparison groups

Am Rev Respir Dis

The value of serial bronchoalveolar lavages in assessing the clinical progress of patients with cryptogenic fibrosing alveolitis

Am Rev Respir Dis

Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy

Thorax

Cryptogenic fibrosing alveolitis: relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis

Am Rev Respir Dis

The eosinophil component of the alveolitis in idiopathic pulmonary fibrosis

Am Rev Respir Dis

Idiopathic pulmonary fibrosis: pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy

Am Rev Respir Dis

Characterization of the inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease

Am Rev Respir Dis

Determinants of survival in idiopathic pulmonary fibrosis

Am J Respir Crit Care Med

Laboratory and Animal Investigations
The Role of Neutrophils in the Pathogenesis of Idiopathic Pulmonary Fibrosis