Ratio In Bronchoalveolar Lavage Fluid Research Articles

Changes in T-cell subsets occur in interstitial lung disease and may contribute to pathology via complicated immune cascade.

The study aimed to investigate the expression profiles of transcription factors, cytokines, and co-stimulatory molecules in helper T (Th)-cell subsets within bronchoalveolar lavage (BAL) samples of patients with interstitial lung diseases (ILDs). Twenty ILDs patients were included in the study, comprising those with idiopathic pulmonary fibrosis (IPF) (n:8), autoimmune-related ILDs (auto-ILD) (n:4), and orphan diseases (O-ILD) (n:8), alongside five control subjects. Flow cytometry was employed to evaluate the Th to cytotoxic Tcell (CTL) ratio in BAL fluid, while cytopathological examination assessed macrophages, lymphocytes, and neutrophils. Quantitative real-time polymerase chain reaction was utilized to investigate the expressions in Th1, Th2, Th17, and regulatory T (Treg) cells. Results revealed elevated Th cell to CTL ratios across all patient groups compared to controls. Furthermore, upregulation of Th1, Th2, Th17, and T-cell factors was observed in all patient groups compared to controls. Interestingly, upregulation of CD28 and downregulation of CTLA-4 and PD-1 gene expression were consistent across all ILDs groups, highlighting potential immune dysregulation. This study provides a comprehensive exploration of molecular immunological mechanisms in ILDs patients, underscoring the dominance of Th2 and Th17 responses and revealing novel findings regarding the dysregulation of CD28, CTLA-4, and PD-1 expressions in ILDs for the first time.

Minimal effective dose of maintenance steroid therapy for relapse of cryptogenic organizing pneumonia

BackgroundLong-term maintenance steroid therapy (MST) is frequently required for repeated relapses of cryptogenic organizing pneumonia (COP); however, the optimal minimal dose has not been clarified. Therefore, this study evaluated the minimal MST dose required to prevent repeated relapses and identify relapse predictors. MethodsWe retrospectively reviewed the medical records of patients with steroid-treated COP and compared background factors between the non-relapse and relapse groups. We also reviewed the treatment course in the relapse group and determined the minimal effective steroid dose based on the MST dose at relapse events and the current relapse prevention dose. ResultsIn total, 48 patients were identified, including 27 (56%) in the non-relapse group and 21 (44%) in the relapse group. Receiver operating characteristic curve analysis identified prednisolone at 5 mg/day as the optimal cut-off value in the relapse group. Relapse-free time in patients with relapsed COP was significantly longer in the MST dose ≥5 mg/day group than in the <5 mg/day group (log-rank P = 0.003; hazard ratio, 0.19; 95% confidence interval [CI], 0.04–0.60). Multivariate logistic regression analysis demonstrated that a high eosinophil percentage and CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) were predictors of relapse (odds ratio [OR], 1.12; 95% CI, 1.02–1.23; P = 0.008 and OR, 3.87; 95% CI, 1.29–11.6; P = 0.008, respectively). ConclusionsOur results indicate that 5 mg/day of prednisolone may be the minimal effective dose for preventing repeated relapses, and a high BALF eosinophil percentage and CD4/CD8 ratio are independent predictors of relapse.

Evaluation of high-resolution computed tomography findings and associated factors in hypersensitivity pneumonitis

Background/Aim: Hypersensitivity pneumonitis (HP) is a lung disease from inhaling diverse environmental and occupational organic substances, such as fungi, bacteria, birds, and occasionally nonorganic materials. An immune response triggers this condition. A high-resolution chest computed tomography (HRCT) scan is typically performed as part of the initial diagnostic assessment. This study assesses HRCT findings in HP patients and examines associated factors between fibrotic and non-fibrotic patient groups. Methods: This retrospective cross-sectional study encompassed all HP patients monitored between 2010 and 2022. The analysis included data from 117 patients. HRCT findings from the patients were categorized based on fibrosis presence, leading to the division of patients into fibrotic and non-fibrotic groups. Comparative analyses were conducted between these groups. Results: Among the 117 subjects analyzed, 59 (50.4%) were male, and 58 (49.6%) were female. The mean age at diagnosis was 52.1 (13.6) years, ranging from 20 to 81. The non-fibrotic HP group comprised 70 (59.8%) patients, while the fibrotic HP group comprised 47 (40.2%). The most prevalent HRCT findings were ground-glass opacity (90.6%), mosaic attenuation (87.2%), and traction bronchiectasis (50.4%). Statistically significant disparities were observed between non-fibrotic and fibrotic HP groups in terms of HRCT findings: ground-glass opacity, irregular linear opacities, reticulation, traction bronchiectasis, honeycombing, and fibrosis (P=0.024, P&lt;0.001). In contrast, the lymphocyte ratio in bronchoalveolar lavage fluid was 28.78 (16.2) in the non-fibrotic HP group and 14.66 (10.3) in the fibrotic HP group. The fibrotic HP group exhibited a statistically significant lower lymphocyte ratio in bronchoalveolar lavage fluid (P&lt;0.001). Conclusion: HRCT findings are pivotal in HP diagnosis and classification. Computed tomography also assists in delineating the HP classification. This study identified ground-glass opacity and mosaic attenuation as the most prevalent HRCT findings in HP patients. Investigating the connection between fibrosis and prognosis is vital for determining patient outcomes, as fibrosis appears to be the principal determinant.

Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

186P Elevated CXCL10:IL-8 ratio in bronchoalveolar lavage fluid of immune checkpoint inhibitor-related pneumonitis

186P Elevated CXCL10:IL-8 ratio in bronchoalveolar lavage fluid of immune checkpoint inhibitor-related pneumonitis

Analysis of lymphocyte profile in lymph nodes, bronchoalveolar lavage fluid and peripheral blood in patients with stage II sarcoidosis

ObjectiveTo evaluate the lymphocyte profile (LP) in lymph node puncture fluid (LNPF) of mediastinal and hilar lymph nodes, bronchoalveolar lavage fluid (BALF), and peripheral blood (PB) involved in stage 2 sarcoidosis. MethodsAfter selection, 31 patients diagnosed with stage II sarcoidosis were finally included. Patients were further divided into symptomatic (n = 17) and asymptomatic (n = 14) groups according to the presence or absence of respiratory symptoms. The LP in lymph node puncture fluid (LNPF), bronchoalveolar lavage fluid (BALF), and peripheral blood (PB) were evaluated and compared using flow cytometry. The relationship between respiratory symptoms and LP was preliminarily analyzed. ResultsThe proportions of T cells and CD4 T cells, and CD4/CD8 ratio in BALF were significantly higher than that of LNPF with PB (all P < 0.05). The proportions of lymphocyte cells, CD8 T cells, NK cells, and CD4/CD8 ratio in LNPF and PB were significantly different (all P < 0.05). There were significant differences in CD4 T cells [72.40 (68.90,75.55) vs.46.30 (38.55,52.50), P = 0.004], CD8 T cells (9.9 ± 3.9 vs. 16.8 ± 6.8, P = 0.002), and CD4/CD8 ratio (7.9 ± 2.8 vs. 3.9 ± 1.5, P < 0.001) in BALF between the symptomatic group and asymptomatic group (all P < 0.05). The T cells (rs = 0.447, P = 0.011), CD4 (rs = 0.572, P = 0.002), and CD4/CD8 ratio (rs = 0.701, P < 0.001) in BALF were positively correlated with respiratory symptoms. ConclusionThe LP in LNPF, BALF and PB were significantly different and the main index correlated with respiratory symptoms was CD4/CD8 ratio in BALF. The difference of LP in BALF and LNPF may help to deeply understand the pathophysiological process and may reflect the different degree of lung and lymph node lesion.

Suppression of NLRP3 inflammasome by Platycodin D via the TLR4/MyD88/NF-κB pathway contributes to attenuation of lipopolysaccharide induced acute lung injury in rats

Acute lung injury (ALI) is a common clinical condition with a high mortality rate and no specific treatment is available. An excessive inflammatory response contributes to the development of ALI and accelerates its progression, and the NLRP3 inflammasome and NF-κB signaling pathways are key players in inflammation. Platycodin D has been reported to have anti-oxidant and anti-stress properties in various diseases. However, the effects of PLD in ALI has not been clearly demonstrated. The aim of this study was to investigate the therapeutic effects of PLD on ALI and its possible mechanism. Our study found that PLD pre-treatment attenuated lung histopathological injury in LPS-induced SD rats and reduced the levels of inflammatory cytokines and lung wet/dry ratio in bronchoalveolar lavage fluid (BALF). In addition, PLD modulate LPS-induced production of MDA, MPO, GSH, GSH-Px and CAT in lung tissue. In addition, PLD suppressed the activation of NLRP3 inflammatory microsomes and the NF-κB signaling pathway. Thus, our results suggest that PLD are protective against LPS-induced ALI by inhibiting NLRP3 and NF-κB signaling pathway.

An update on the diagnosis and management of ocular sarcoidosis.

Ocular sarcoidosis is one of the most common causes of uveitis worldwide. The diagnosis and treatment of patients with ocular sarcoidosis remains challenging in some cases. It is important for clinicians to keep up to date with new diagnostic and treatment tools for this disease. The International Workshop on Ocular Sarcoidosis diagnostic criteria were first proposed in 2009 and revised in 2017. The new criteria contained two parts: ocular presentation and systemic investigation. The diagnostic value of liver enzymes was reduced in the new criteria, whereas the value placed of lymphopenia and the CD4/CD8 ratio in bronchoalveolar lavage fluid were increased. Despite not being included in the criteria, recent studies have also highlighted the diagnostic value of serum soluble interleukin-2 receptors. Recent ophthalmologic imaging also provides useful insights for the differential diagnosis.Many new treatments for ocular sarcoidosis have been developed in recent years. The introduction of biological immunomodulatory agents for uveitis treatment represents a big improvement. Antitumor necrosis factor-alpha antibodies, including adalimumab, have been proven to be effective for treating ocular sarcoidosis. Many studies have also suggested that other biological agents could be effective and well tolerated. Newer intravitreal dexamethasone and fluocinolone implants have been developed. Patients treated with these implants have experienced good and sustained control of their intraocular inflammation. Diagnosis and treatment options for ocular sarcoidosis have changed over time. However, challenges still exist in some difficult patients. Future studies should focus on finding more sensitive biomarkers and developing more effective immunomodulatory treatments with longer efficacy and less side effects.

Clinical efficacy of Baihe Gujin decoction combined with anti-tuberculosis therapy for pulmonary tuberculosis with Yin-deficiency and Fire-hyperactivity syndrome.

ObjectiveTo evaluate the clinical efficacy of Baihe Gujin decoction combined with anti-tuberculosis therapy in mitigating the symptoms of pulmonary tuberculosis and to measure the effect on the CD4+ CD25+ regulatory T cell (Treg) ratio.MethodsThis randomized study enrolled patients with pulmonary tuberculosis and randomly assigned them to one of two treatment groups: an anti-tuberculosis treatment group and a combined treatment group. Bronchoalveolar lavage was performed before and 2 weeks after treatment. The ratio of CD4+ CD25+ Treg cells and the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4, IL-6 and IL-12 in peripheral blood and bronchoalveolar lavage fluid were measured. Symptoms were recorded before and after treatment.ResultsA total of 100 patients were enrolled and assigned to the anti-tuberculosis (n = 58) and combined treatment groups (n = 42). In the combined treatment group, Leicester Cough Questionnaire score, erythrocyte sedimentation rate, CD4+ CD25+ Treg cell ratio in bronchoalveolar lavage fluid, cytokine levels, chest pain score and sleep disorder score were significantly decreased compared with the anti-tuberculosis treatment group after treatment. The leukocyte count, haemoglobin level, platelet and alanine aminotransferase levels did not differ significantly between the two groups after treatment. The creatinine level in the combined treatment group was significantly lower than that in the anti-tuberculosis treatment group.ConclusionBaihe Gujin decoction combined with anti-tuberculosis treatment can effectively alleviate the symptoms of pulmonary tuberculosis, enhance the host immune function and protect renal function.

Treadmill exercise restores memory and hippocampal synaptic plasticity impairments in ovalbumin-sensitized juvenile rats: Involvement of brain-derived neurotrophic factor (BDNF)

Studies demonstrate that asthma, especially during childhood, affects the functions of the brain including learning and memory. Exercise is well known for its neuroprotective functions and for its beneficial effects on asthma. We aimed to assess the effects of exercise on cognitive function, synaptic plasticity, and hippocampal brain-derived neurotrophic factor (BDNF) levels in ovalbumin (OVA) sensitized juvenile rats. Rats were sensitized by intraperitoneal administration and inhaled OVA. Animals were subjected to treadmill running exercise during the OVA-challenged period. T-helper type 2 (Th2) cytokine [interleukin (IL)-4], Th1 cytokine (INF-γ) levels, and INF-γ/IL-4 (Th1/Th2) ratio in bronchoalveolar lavage fluid (BALF), and tracheal response to methacholine and OVA were measured. Further, memory behaviors and BDNF levels were measured in the hippocampus as well as long-term potentiation (LTP) was assessed by recording field excitatory postsynaptic potentials (fEPSPs) in the hippocampus. The levels of IL-4 and TGF-β were decreased but INF-γ level and INF-γ/IL-4 ratio increased in the BALF due to exercise in the OVA-sensitized animals. In addition, exercise improved OVA-sensitization induced cognitive impairments, increased BDNF levels, and enhanced hippocampal LTP in OVA-sensitized rats. Exercise is not only effective in the alleviation of airway inflammation by restoring Th1/Th2 cytokines balance, but also is a candidate for improvement of memory and synaptic plasticity deficits partially through increasing the levels of hippocampal BDNF in OVA-sensitized rats.

Retrospective Study of Factors Potentially Influencing Occurrence of Cough in Slovak Patients with Sarcoidosis.

Introduction Sarcoidosis is a multisystem granulomatous disease of unknown aetiology, commonly involving the lungs. Cough is a frequent and troublesome symptom of sarcoidosis that reduces patients' quality of life. Aim Retrospective analysis of different factors—smoking history, Scadding stage, results of lung function testing, calcium metabolism, endobronchial finding, CD4+/CD8+ T-cell ratio in bronchoalveolar lavage fluid (BALF), and other sarcoidosis symptoms in relationship to presence/absence of cough in sarcoidosis patients. Methods We retrospectively studied sarcoidosis patients diagnosed at the Clinic of Pneumology and Phthisiology of Martin University Hospital between 1998 and 2018. Patients with a history of cough-relevant comorbidities were excluded from the study. GraphPad Prism 7.0 software was used to perform statistical analysis. Results 101 sarcoidosis patients were included to the study: 65 patients reporting from cough and 36 without cough. The cough was slightly more frequent in nonsmokers (p=0.166) and in women (p=0.688). Cough was associated with dyspnoea (p=0.0007), fever (p=0.0324), and chest pain (p=0.0206) and did not associate with arthralgia (p=0.317) and erythema nodosum (p=0.505). Patients with cough had significantly a lower average value of calciuria (p=0.0014) and lower MEF25 (p=0.0304), MEF50 (p=0.0061), FEV1 (p=0.0025), and FVC (p=0.0025) in % of predicted values, and more often positive endobronchial finding (p=0.0206), compared to patients without cough. Calcemia, FEV1/FVC, DLCO, and CD4+/CD8+ T-cell ratio in BALF and occurrence of cough did not differ between different stages of the disease. Conclusions We found significant differences between sarcoidosis patients with/without cough regarding symptoms, results of lung function tests, endobronchial finding, and calcium metabolism. Further research is needed to understand the etiopathogenesis of cough in sarcoidosis patients.

Periostin as a predictor of prognosis in chronic bird-related hypersensitivity pneumonitis

BackgroundPeriostin is an established biomarker of Th2 immune response and fibrogenesis. Recent research has indicated that periostin plays an important role in the pathogenesis of idiopathic interstitial pneumonias. To clarify the relationship between periostin and pathogenesis in chronic bird-related hypersensitivity pneumonitis (HP) and to reveal the usefulness of serum periostin levels in diagnosing and managing chronic bird-related HP. MethodsWe measured serum periostin in 63 patients with chronic bird-related HP, 13 patients with idiopathic pulmonary fibrosis, and 113 healthy volunteers. We investigated the relationship between serum periostin and clinical parameters, and evaluated if the baseline serum periostin could predict the prognosis. ResultsSerum periostin was significantly higher in patients with chronic bird-related HP compared to the healthy volunteers. In chronic bird-related HP, serum periostin had significant positive correlations with serum KL-6 levels, the CD4/CD8 ratio in bronchoalveolar lavage fluid, and fibrosis score on HRCT, and a significant negative correlation with the diffusing capacity of the lungs for carbon monoxide. Chronic bird-related HP patients with serum periostin levels exceeding ≥92.5 ng/mL and ≥89.5 ng/mL had a significantly worse prognosis and significantly higher frequency of acute exacerbation, respectively. Higher serum periostin (92.5 ng/mL or higher; binary response for serum periostin) was an independent prognostic factor in multivariate analysis. ConclusionsSerum periostin may reflect the extent of lung fibrosis and play an important role in pathogenesis of chronic bird-related HP. Elevated serum periostin could be a predictor of prognosis in patients with chronic bird-related HP.

Galactomannan detection in bronchoalveolar lavage fluid corrected by urea dilution for the diagnosis of invasive pulmonary aspergillosis among nonneutropenic patients.

To investigate the diagnostic performance of galactomannan (GM) detection in bronchoalveolar lavage fluid (BALF) corrected by urea dilution and modification of the AspICU clinical algorithm. GM detection in serum and BALF samples was performed in nonneutropenic patients on the day of clinically suspected invasive pulmonary aspergillosis (IPA) between January 2016 and June 2018, and urea was measured in the plasma and BALF. The BALF GM concentration was corrected by urea dilution, and receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value. A total of 184 patients who were suspected of IPA, were enrolled in this prospective study together with 30 patients with lung cancer as a control group. Seventy-eight patients were diagnosed with IPA, including 37 who were verified by pathology. The urea plasma-to-urea BALF ratio in the IPA group [4.18 (IQR, 3.52-4.91)] was greater than that in the non-IPA group [3.42 (IQR, 3.12-3.76), P<0.001]. The ROC curve showed that defining the cut-off value as 2.94 optical density index (ODI) for the corrected BALF GM resulted in a sensitivity and specificity of 85.91% and 94.07%, respectively, and was more accurate than the use of the uncorrected values (P<0.05). The corrected BALF GM was valuable for diagnosing IPA in nonneutropenic patients. The modified AspICU clinical algorithm based on this measurement represents a reliable diagnostic instrument in clinical settings.

Determination of CD4, CD8, and IL-8 levels in serum and bronchoalveolar lavage fluid of anthracosis patients

Background: Anthracosis is a chronic pulmonary disease with black pigmentation of the bronchial mucosa, caused by carbon accumulation in the lungs, and in some cases, associated with pulmonary tuberculosis (TB). The purpose of this study is to evaluate the serum and bronchoalveolar lavage (BAL) fluid levels of the CD4/CD8 ratio and interleukin 8 (IL-8), as the potential diagnosis and prognosis biomarkers for anthracosis. Methods: Of 60 patients, referred to the Masih Daneshvari Hospital, 30 anthracosis patients, confirmed by bronchoscopy, were included as the case group. BAL sample and blood samples were collected from all individuals and sent to the immunology laboratory. Patients with no anthracosis on bronchoscopy, and suspected to have TB, were included in the control group. In addition, BAL samples were used for BK-polymerase chain reaction. Results: In this case–control study, 30 anthracosis patients and 30 controls were investigated. There were no significant differences in IL-8 of patients with anthracosis, compared to others. There were significant differences of the CD4/CD8 ratio in BAL fluid, between anthracosis cases and the control group (1.01 ± 0.77 vs. 2.41 ± 3.50; P = 0.04), and significant differences were seen in serum levels of two groups (P = 0.02). The rate of the confirmed pulmonary TB which was 88.9% in patients with anthracosis was significantly higher than the control group. Conclusion: These outcomes suggest that changes in the CD4/C8 levels in serum and BAL fluid may have a leading role in the diagnosis or prognosis of anthracosis. In addition, due to the strong association of anthracosis and pulmonary TB, TB should be considered in patients with anthracosis, which in turn can eventuate to the early distinguish and cure of the patients.

Clinical characteristics of patients with anti-aminoacyl-tRNA synthetase antibody positive idiopathic interstitial pneumonia.

Anti-aminoacyl-tRNA synthetase (ARS) antibodies have been detected in patients with polymyositis/dermatomyositis (PM/DM) and are especially correlated with interstitial lung disease (ILD). The aim of this study was to clarify the clinical features of patients with anti-ARS antibody positive idiopathic interstitial pneumonias (IIPs). Patients were classified into three groups: 1) IIP with anti-ARS antibodies (ARS(+)IIP), 2) IIP without anti-ARS antibodies (ARS(-)IIP), and 3) PM/DM-associated ILD with anti-ARS antibodies (ARS(+)PM/DM-ILD). Clinical characteristics were compared retrospectively between the ARS(+)IIP group and the ARS(-)IIP group or ARS(+)PM/DM-ILD group. Eighteen ARS(+)IIP, 284 ARS(-)IIP, and 20 ARS(+)PM/DM-ILD patients were enrolled. The ARS(+)IIP group was significantly older and the male sex was predominant, had a lower prevalence of signs of connective tissue disease, differences in HRCT findings and patterns, and higher KL-6 levels compared to the ARS(+)PM/DM-ILD group. The findings in the bronchoalveolar lavage fluid (BALF) showing lymphocytosis and a lower CD4/CD8 ratio were similar between the two groups. However, the ARS(+)IIP group had significantly lower percentage of sputum, higher prevalence of mechanic's hand, higher KL-6 levels, lower percentage of vital capacity in the pulmonary function test, and lower CD4/CD8 ratio in BALF, compared to the ARS(-)IIP group. The present study demonstrated that features of pulmonary involvement were similar to those in the ARS(+)PM/DM-ILD group; however, some differences including HRCT findings and higher KL-6 levels suggest that ARS(+)IIP has severe ILD compared with ARS(+)PM/DM-ILD. Further prospective studies with a larger number of patients will elucidate the exact role of anti-ARS antibodies in IIPs.

Japanese herbal medicine-induced pneumonitis: A review of 73 patients.

The number of reports concerning Japanese herbal medicine (JHM)-induced pneumonitis has increased. However, comprehensive data are lacking in this regard, and the clinical characteristics of the disease remain unclear. A literature review was performed using PubMed and Ichushi-Web-the database of the Japan Medical Abstracts Society-to identify articles published between 1996 and 2015 describing patients with JHM-induced pneumonitis. The final cohort included 73 patients in 59 articles (7 in English; 52 in Japanese). Among the various JHMs reported, sho-saiko-to was the most frequently used drug (26%), followed by sairei-to (16%), seishin-renshi-in (8%), and bofu-tsusyo-san (8%). These drugs commonly contain ougon (skullcap) and kanzo (liquorice). The mean age at pneumonitis diagnosis was 63.2 ± 15.5 years (range: 7-89 years). The male/female ratio was 44/29. Sixty-five patients (89%) developed pneumonitis within 3 months of beginning JHM treatment. Bilateral ground-glass attenuations on chest computed tomography, as well as lymphocytosis with a low CD4/CD8 T-cell ratio in bronchoalveolar lavage fluid, were common findings. Twenty-six patients (36%) recovered from the pneumonitis after simply discontinuing the causative JHM. However, the remainder required immunosuppressive therapy, and 13 patients (18%) received mechanical ventilation. Importantly, three patients (4%) did not survive, with two showing pathological diffuse alveolar damage upon autopsy. Clinicians should be cautious regarding JHM-induced pneumonitis, particularly when using drugs/ingredients known to cause this complication, and during the early treatment period. Although most events are non-severe, critical cases should be recognized.

The expression and clinical role of KL-6 in serum and BALF of patients with different diffuse interstitial lung diseases

To detect the levels of KL-6 in the serum and the bronchoalveolar lavage fluid (BALF) of patients with different type of diffuse interstitial lung diseases(DILD), and to analyze its correlation with pulmonary function, pulmonary HRCT scores and other parameters. Seventy-three patients with DILD were enrolled, including 34 patients with idiopathic pulmonary fibrosis (IPF), 10 patients with stage Ⅰ sarcoidosis(SAR Ⅰ), 15 patients with hypersensitivity pneumonia (HP), 14 patients with connective tissue diseases (CTD). Enzyme-linked immune sorbent assay (ELISA) was used to detect the levels of KL-6 in the serum and the BALF of these patients. In the IPF group, FVC predicted percentage and DLCO predicted percentage were significantly lower than those of the SAR Ⅰ group[(70±14)% vs (82±6)%, (49±13)% vs(81±6)%, P<0.05], but were no different compared to the CTD-ILD group(P>0.05). In the IPF group, the percentage of neutrophils in BALF was higher than that of the SAR Ⅰ group[(9±7)% vs (6±4)%, P<0.05]], and the percentage of lymphocytes and CD4/CD8 ratio in BALF were lower than those of the SAR Ⅰ group[(12±7)% vs (23±13)%, (1.5±0.8) vs(4.0±5.1), P<0.05]. In the IPF group, the level of KL-6 in serum was higher than that of the SAR Ⅰ and the HP group[(858±516)U/ml vs (339±168)U/ml, (553±287)U/ml, P<0.05], but was no different compared to the CTD-ILD group (P>0.05). In the CTD-ILD group, the level of KL-6 in serum was higher than that of the SAR Ⅰ [(687±350) U/ml vs (339±168)U/ml, P<0.05]]. In the IPF group, the level of KL-6 in BALF was (437±252)U/ml, and was higher than that of other 3 groups(P<0.05). In the IPF group, the level of serum KL-6 was negatively correlated with FVC and DLCO(r=-0.46, -0.58, P<0.01), the level of serum KL-6 was positively correlated with pulmonary HRCT reticular pattern and honeycombing scores(r=0.62, 0.41, P<0.05). In patients with IPF, the levels of KL-6 in serum and BALF were increased and the level of KL-6 in serum was correlated with FVC, DLCO and pulmonary HRCT reticular pattern and honeycombing scores.KL-6 may be a marker for the diagnosis of IPF.

Interstitial lung disease in clinically amyopathic dermatomyositis with and without anti-MDA-5 antibody: to lump or split?

BackgroundInterstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM-ILD) is often refractory and rapidly progressive. Although the anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibody is associated with rapidly progressive ILD (RP-ILD), differences in clinical features and prognosis of anti-MDA-5 antibody-positive and -negative CADM-ILD remain unclear.MethodsTo clarify the differences in the clinical features and prognosis between anti-MDA-5 antibody-positive and -negative cases, we retrospectively reviewed the medical records of patients diagnosed with CADM-ILD with and without anti-MDA-5 antibody at Kurashiki Central Hospital from January 2005 to September 2014.ResultsAnti-MDA-5 antibody was found in 10 of 16 patients (63 %). The levels of Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) at the first visit were significantly lower in positive patients than in negative patients, whereas the levels of aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP), and the CD4+/CD8+ ratio in the bronchoalveolar lavage (BAL) fluid were significantly higher in positive patients than negative patients. Subpleural ground-glass opacity (GGO) or irregular linear opacity was predominant in positive patients. Peribronchovascular consolidation was predominant in negative patients. Positive patients had significantly lower survival rates than negative patients, with all six fatal cases occurring in positive patients who died of refractory ILD within 92 days from the first visit despite intensive treatment.ConclusionsThere are clear differences in the clinical features and prognosis of anti-MDA-5 antibody-positive and -negative CADM-ILD. Low serum KL-6 and SP-D levels, high serum AST and γ-GTP levels, high CD4+/CD8+ ratio in BAL fluid, and predominance of subpleural GGO or irregular linear opacity in HRCT may help to discriminate anti-MDA-5 antibody-positive CADM-ILD with poor prognosis.

The relative balance of GM-CSF and TGF-β1 regulates lung epithelial barrier function.

Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-β1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-β1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-β1 alone caused an ∼ 25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions ("spikes") containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼ 20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-β1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-β1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-β1. Critically, patients who survived had significantly higher GM-CSF/TGF-β1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-β1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-β1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS.

The Ratio of Free to Bound Desmosine and Isodesmosine May Reflect Emphysematous Changes in COPD.

The unique elastin crosslinks, desmosine and isodesmosine (DID) are significantly elevated in blood, urine, and sputum from patients with COPD, and may decline following treatment of the disease. However, the large degree of variance in this biomarker among COPD patients with similar levels of disease suggests that it has limited prognostic value with regard to the degree of lung disease in a given individual. As an alternative to measuring the total amount of DID, we propose using the ratio of free to peptide-bound DID, which may provide a better indication of overall lung disease. To test this hypothesis, the free/bound DID ratio was measured in bronchoalveolar lavage fluid (BALF) from both hamsters with elastase-induced emphysema and controls not given the enzyme, using a combination of liquid chromatography and tandem mass spectroscopy. This ratio was then correlated with airspace enlargement, as measured by the mean percentage of lung surface area at ×100 microscopic magnification. There was a significant negative correlation between the free/bound DID ratio in BALF and lung surface area. However, there was no correlation between this ratio and total BALF DID, suggesting that free/bound DID is unrelated to the immediate rate of breakdown of elastic fibers, and may instead measure the cumulative effect of elastase injury in the lung. The free/bound DID ratio may be a useful measure of emphysematous changes in the lung and might also serve as a screening procedure for healthy smokers and other individuals at risk for developing COPD.