Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis
Abstract Background Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the sma...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | https://doi.org/10.1186/s12890-023-02837-2 |
| _version_ | 1797355963127169024 |
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| author | Lígia Pelosi Mendonça Natalia de Souza Xavier Costa Ellen Caroline Toledo do Nascimento Martina Rodrigues de Oliveira Carlos Roberto Ribeiro de Carvalho Bruno Guedes Baldi Marisa Dolhnikoff |
| author_facet | Lígia Pelosi Mendonça Natalia de Souza Xavier Costa Ellen Caroline Toledo do Nascimento Martina Rodrigues de Oliveira Carlos Roberto Ribeiro de Carvalho Bruno Guedes Baldi Marisa Dolhnikoff |
| author_sort | Lígia Pelosi Mendonça |
| collection | DOAJ |
| description | Abstract Background Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). Methods Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-β expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. Results The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. Conclusion LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS). |
| first_indexed | 2024-03-08T14:19:47Z |
| format | Article |
| id | doaj.art-0a82c926b93c45faa721802526b94da1 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-03-08T14:19:47Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-0a82c926b93c45faa721802526b94da12024-01-14T12:07:31ZengBMCBMC Pulmonary Medicine1471-24662024-01-0124111110.1186/s12890-023-02837-2Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosisLígia Pelosi Mendonça0Natalia de Souza Xavier Costa1Ellen Caroline Toledo do Nascimento2Martina Rodrigues de Oliveira3Carlos Roberto Ribeiro de Carvalho4Bruno Guedes Baldi5Marisa Dolhnikoff6Departamento de Patologia, Faculdade de Medicina, Universidade de Sao PauloDepartamento de Patologia, Faculdade de Medicina, Universidade de Sao PauloDepartamento de Patologia, Faculdade de Medicina, Universidade de Sao PauloDivisao de Pneumologia, Instituto do Coracao (InCor), Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de Sao PauloDivisao de Pneumologia, Instituto do Coracao (InCor), Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de Sao PauloDivisao de Pneumologia, Instituto do Coracao (InCor), Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de Sao PauloDepartamento de Patologia, Faculdade de Medicina, Universidade de Sao PauloAbstract Background Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). Methods Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-β expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. Results The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. Conclusion LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).https://doi.org/10.1186/s12890-023-02837-2LymphangioleiomyomatosisSmall airwaysPulmonary function testLAM ScoreImmunohistochemistry |
| spellingShingle | Lígia Pelosi Mendonça Natalia de Souza Xavier Costa Ellen Caroline Toledo do Nascimento Martina Rodrigues de Oliveira Carlos Roberto Ribeiro de Carvalho Bruno Guedes Baldi Marisa Dolhnikoff Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis BMC Pulmonary Medicine Lymphangioleiomyomatosis Small airways Pulmonary function test LAM Score Immunohistochemistry |
| title | Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis |
| title_full | Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis |
| title_fullStr | Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis |
| title_full_unstemmed | Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis |
| title_short | Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis |
| title_sort | small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis |
| topic | Lymphangioleiomyomatosis Small airways Pulmonary function test LAM Score Immunohistochemistry |
| url | https://doi.org/10.1186/s12890-023-02837-2 |
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