BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases (original) (raw)

Comparison of lymphocyte immune phenotypes in bronchoalveolar lavage of non-smoking patients with sarcoidosis and other interstitial lung diseases

Journal of Thoracic Disease, 2019

Background: Bronchoalveolar lavage (BAL) as complementary method is still used as ancillary tool in diagnosis of interstitial lung diseases. Tobacco smoking has been described to affect the BAL lavage cellular profile. To our knowledge, only few reports have so far investigated CD3 + CD4 + and CD3 + CD8 + lymphocyte subsets in non-smoking sarcoidosis patients additionally stratified according to CXR stage, and compared them to other non-smoking patients with interstitial lung diseases (ILDs). Methods: We compared lymphocytes immune phenotypes, subsets, with CD3 + , CD3 + CD4 + and CD3 + CD8 + cell markers, in the non-smoking subjects (n=297) including the patients with pulmonary sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) (n=22), hypersensitivity pneumonitis (HP) (n=15), other interstitial idiopathic pneumonias (OIIPs) (n=39). According to prognosis, the patients with S were divided into four groups: 18 patients with Löfgren's syndrome (LS) in chest X-ray (CXR) ≤1 stage, 64 patients without LS in CXR ≤1 stage, 113 patients in CXR 2 stage and 26 patients with advanced CXR ≥3 stage. Results: After the use of false discovery rate (FDR) correction, relative numbers (%) of CD3 + , CD3 + CD4 + , CD3 + CD8 + and CD3 + CD4 + /CD3 + CD8 + ratio showed the most significant differences between the nonsmokers with S (both with/without LS) and the non-smokers with other ILDs (IPF, OIIPs, HP). These lymphocytes subsets were further altered in the non-smokers with CXR stage 2 compared to the nonsmokers with other ILDs (IPF, OIIPs, HP). We did not observe any differences in these lymphocyte subsets and CD3 + CD4 + /CD3 + CD8 + ratio between the non-smokers with advanced sarcoidosis stage (CXR ≥3) and the non-smokers with IPF. Conclusions: Our data on the non-smokers confirmed the presence of the typical BAL cellular profile in sarcoidosis. The BAL cellular profile was helpful namely for differentiation of less advanced sarcoidosis. Its definite diagnostic utility should be the subject of further clinical studies with large numbers of the well characterized patients taking into consideration other clinical factors influencing BAL cellular profile, such as smoking or treatment.

Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases

European Respiratory Journal, 2004

The current authors aimed to quantify how the likelihood for a given diagnosis changes with the knowledge of bronchoalveolar lavage (BAL) cell differentials. As an initial estimate (a priori probability), frequencies of final diagnoses were taken. Using categorisations for cell differentials, a posteriori probabilities were then derived for each disease, according to Bayes. The analysis was performed in three of five groups of diagnoses suspected prior to BAL: interstitial lung disease (ILD; n=710), inflammatory disease (n=583), or lung tumour mimicking ILD (n=455). Overall, out of 1,971 patients, 18.3% had sarcoidosis, 7.7% usual interstitial pneumonia (UIP), 4.4% extrinsic allergic alveolitis (EAA), and 19.0% tumours. In the group with suspected ILD, the likelihood for sarcoidosis increased from 33.7 to 68.1% when lymphocyte numbers were 30-50% and granulocyte numbers were low; the likelihood for UIP increased from 15.8 to 33.3% when lymphocyte numbers werev30% with granulocytes elevated. CD4/CD8 was informative, especially in sarcoidosis and EAA. Despite considerable increases, the likelihood of rare diseases rarely reached appreciable values. Similar results were obtained in the other two groups of suspected diagnoses. In conclusion, these data suggest that bronchoalveolar lavage cell counts per se provide substantial diagnostic information only in relatively frequent diseases, such as sarcoidosis and usual interstitial pneumonia, and are less helpful in infrequent diseases.

CD4:CD8 Ratio: A Valuable Diagnostic Parameter for Pulmonary Sarcoidosis

2018

Summary Sarcoidosis is a multi-organ disease and is characterized by sarcoidal noncaseating granuloma comprised of T-helper/inducer (CD4+) lymphocytes and scant cytotoxic (CD8+) T-lymphocytes. CD4+:CD8+ T-cell elevated ratio is a characteristic diagnostic parameter for sarcoidosis. This is the first report from Iran evaluating the CD4:CD8 ratio capability in differentiating pulmonary sarcoidosis from other interstitial lung diseases (ILDs) on a large cohort. Fifty pulmonary sarcoidosis patients and 50 non-sarcoidosis interstitial lung diseases (nsILDs) patients were included in the current study. Bronchoalveolar lavage (BAL) was performed using flexible fiberoptic bronchoscopy and flow cytometer. Non-sarcoidosis group was established by 50 components that were classified into eight subgroups. Fifty-two percent of sarcoidosis patients and 62% of non-sarcoidosis interstitial lung disease patients had normal spirometric results. The CD4/CD8 ratio was significantly higher in sarcoidosis...

Relationship between presentation of sarcoidosis and T lymphocyte profile. A study in bronchoalveolar lavage fluid

CHEST Journal, 1993

One hundred patients with histologically verified sarcoidosis were studied. They were divided into three groups, based on their clinical presentation and smoking status. Group A consisted ofpatients whose disease was detected by routine chest x-ray film, without symptoms; grcop B included those with respiratory and general constitational symptoms; and group C included patients with erythema nodosum and/or arthralgia and hilar lymphadenopathy. Group A showed an increased CD4/CD8 ratio of4.7±1.1; group B, 8.0± 1.2; ' In addition to granuloma formation, there is often an extensive vascular disease as seen by the appearance of microangiopathies. Granulorna formation in the lungs is preceded by a mononuclear cell alveolitis with increased numbers of activated T lymphocytes and alveolar macrophages. 7 Besides changes in T lymphocyte and alveolar macrophage populations, changes in the humoral immunity have been reported.8 Clinical manifestations ofsarcoidosis depend on the intensity of the inflammation and organ systems affected.mm.11 In some sarcoidosis patients, the alveolitis remains subclinical, whereas in others both alveolitis and granuloma formation are present, resulting in specific pulmonary symptoms.'2'4 Although the lung is the most frequently affected organ, extrapulmonary manifestations such as erythema nodosum commonly occur. 1.3,10 Bronchoalveolar lavage (BAL) is regarded as an important diagnostic method in

Diagnostic role of BAL fluid CD4/CD8 ratio in different radiographic and clinical forms of pulmonary sarcoidosis

Clinical Respiratory Journal, 2009

Introduction: Bronchoalveolar lavage (BAL) as a method of sampling cells is useful in the diagnosis and differential diagnosis of sarcoidosis. However, CD4/CD8 ratio in BAL fluid (BALF) is highly variable and it generates continuous discussions about its diagnostic role.Objective: To prospectively evaluate diagnostic role of BALF CD4/CD8 ratio in pulmonary sarcoidosis manifested in different radiographic and clinical forms in the real clinical practice.Material and methods: The study population consisted of 318 sarcoid patients with a newly diagnosed disease. Comparator groups consisted of 55 healthy subjects and 130 patients with other disorders who underwent BAL and examination of CD4/CD8 ratio in BALF as a step of diagnostic pathway. Diagnostic accuracy of CD4/CD8 ratio in BALF using receiver-operating characteristic analysis has been calculated.Results: The percentage of BALF lymphocytes in sarcoid patients was significantly different from comparator groups. Normal BALF cell counts were found in 7% of sarcoid patients. However, typical sarcoid BALF cellular pattern was found in 6.2% of all control subjects. We have found that optimal cutoff points for CD4/CD8 ratio are 3.5 and 4.0 for asymptomatic and symptomatic patients, respectively. Sensitivity of the optimal cutoff points of CD4/CD8 ratio was lower in asymptomatic patients compared with symptomatic patients. Sensitivity of the optimal cutoff points decreased with the increased stage of sarcoidosis.Conclusions: BAL is a valuable method in diagnostic pathway of pulmonary sarcoidosis. However, results of BALF examination must be interpreted considering a specific clinical case. BALF CD4/CD8 ratio depends on clinical and radiographic manifestation.Please cite this paper as: Danila E, Norkūnienė J, Jurgauskienė L and Malickaitė R. Diagnostic role of BAL fluid CD4/CD8 ratio in different radiographic and clinical forms of pulmonary sarcoidosis. The Clinical Respiratory Journal 2009; 3: 214–221.

Lymphocyte Subsets and Pulmonary Nodules to Predict the Progression of Sarcoidosis

Biomedicines

The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis, remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. A 2-year follow-up of the study population after the initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF) and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was performed. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the...