Loss Of Pulmonary Function Research Articles

How to identify intersegmental planes in performing sublobar anatomical resections.

Pulmonary segmentectomy is a common surgical procedure in thoracic surgery nowadays. Though this technique helps preventing postoperative pulmonary function loss, potential challenges are the management of air leaks and the difficulty of palpating ground-glass components during surgery, as well as how to deal with the intersegmental planes. Several techniques have been proposed for the identification and treatment of the intersegmental planes during sublobar anatomical resections: this review focuses on preoperative planning and workup and intraoperative strategies. Three-dimensional computed tomography bronchography and angiography (3D-CTBA), virtual-assisted mapping (VAL-MAP) using bronchoscopy multi-spot dye marking and three-dimensional computed tomography (3D-CT) are preoperative tools that may facilitate the planning of operation. Inflation-deflation techniques, infrared-fluorescence-enhanced method combined with bronchial and intravenous injection of indocyanine green (ICG) and near-infrared fluorescence (NIF) mapping with ICG have been described as intraoperative strategies to identify the intersegmental plane. The treatment and section of the intersegmental planes is mainly accomplished by stapler and electrocautery or energy devices. The use of staplers reduces postoperative air leaks, bleeding risks and operative time but seems to reduce preserved lung volume, compromising adjacent lung expansion; in addition, higher costs and sometimes non-adequate oncological margins, being a non-anatomical technique have been described. The electrocautery and energy devices allow for a more anatomical and precise dissection maintaining safe oncological margins, with a better lung expansion and so an increased postoperative lung function. Time consuming procedure and frequent requirement of aero-haemostatic tools to treat air and blood leaks are the main drawbacks. In conclusion, there are several methods to identify and treat the intersegmental planes but there are no significant differences between the different tools, therefore the use of one technique rather than another depends overall on surgeon’s preference and the location of the segment.

How to identify intersegmental planes in performing sublobar anatomical resections

Pulmonary segmentectomy is a common surgical procedure in thoracic surgery nowadays. Though this technique helps preventing postoperative pulmonary function loss, potential challenges are the management of air leaks and the difficulty of palpating ground-glass components during surgery, as well as how to deal with the intersegmental planes. Several techniques have been proposed for the identification and treatment of the intersegmental planes during sublobar anatomical resections: this review focuses on preoperative planning and workup and intraoperative strategies. Three-dimensional computed tomography bronchography and angiography (3D-CTBA), virtual-assisted mapping (VAL-MAP) using bronchoscopy multi-spot dye marking and three-dimensional computed tomography (3D-CT) are preoperative tools that may facilitate the planning of operation. Inflation-deflation techniques, infrared-fluorescence-enhanced method combined with bronchial and intravenous injection of indocyanine green (ICG) and near-infrared fluorescence (NIF) mapping with ICG have been described as intraoperative strategies to identify the intersegmental plane. The treatment and section of the intersegmental planes is mainly accomplished by stapler and electrocautery or energy devices. The use of staplers reduces postoperative air leaks, bleeding risks and operative time but seems to reduce preserved lung volume, compromising adjacent lung expansion; in addition, higher costs and sometimes non-adequate oncological margins, being a non-anatomical technique have been described. The electrocautery and energy devices allow for a more anatomical and precise dissection maintaining safe oncological margins, with a better lung expansion and so an increased postoperative lung function. Time consuming procedure and frequent requirement of aero-haemostatic tools to treat air and blood leaks are the main drawbacks. In conclusion, there are several methods to identify and treat the intersegmental planes but there are no significant differences between the different tools, therefore the use of one technique rather than another depends overall on surgeon's preference and the location of the segment.

Clinical Effect of Pedicled Pericardial Fat Flap in Prevention of Bronchial Pleural Fistula in Bronchial Sleeve Lobectomy

背景与目的支气管袖式肺叶切除是中心型肺癌重要的手术方式，它是最能体现“最大程度切除肿瘤，同时最大程度保留肺功能”的肺癌手术原则。支气管胸膜瘘是支气管袖式肺叶切除最严重的手术并发症，严重威胁患者的生命安全。本文将总结带蒂心包脂肪垫包裹支气管吻合口在预防支气管袖式肺叶切除术后支气管吻合口瘘的临床效果。方法回顾性分析四川大学华西医院肺癌中心2016年1月-2019年5月期间行支气管袖式肺叶切除术，并用带蒂心包脂肪垫包裹支气管吻合口的39例中心型肺癌患者临床资料，观察该组患者术后并发症，尤其是支气管吻合口相关并发症发生情况。结果该组患者手术后恢复良好，均于术后6 d-14 d内出院；30 d内无支气管胸膜瘘发生，无因胸腔内出血再次行手术病例，无严重心律失常，无严重肺部感染及呼吸衰竭发生；术后继续随访期间，术后6个月发生重度吻合口狭窄导致术侧残余肺不张1例。结论支气管袖式肺叶切除的肺癌患者，术中用带蒂心包脂肪垫包裹支气管吻合口，可有效预防术后吻合口瘘相关并发症的发生，从而提高手术安全性。

SUN-134 Estrogen Induces Granulocytic Myeloid Derived Suppressor Cell Production to Potentially Modulate Lymphangioleiomyomatosis (LAM) Tumor Progression

Affecting almost exclusively women, lymphangioleiomyomatosis (LAM) is a rare lung disease characterized by estrogen-sensitive metastatic smooth muscle cell-like adenomas that grow slowly, resulting in cystic lung change and loss of pulmonary function. LAM tumors are caused by mutations in tuberous sclerosis complex 1 or 2 genes (TSC1 or TSC2). Mutations in TSC1 or TSC2 genes results in deficient inhibitory regulation of the mammalian target of rapamycin complex 1 (mTORC1), which in turn leads to increased mTORC1 activity and cell proliferation. There is no consensus amongst LAM researchers regarding the origin of these estrogen receptor-positive smooth muscle like LAM cells; however, we previously reported inactivation of TSC2 in the mouse uterus results in notable LAM features in the setting of primary myometrial tumors. Approximately 50% of the TSC2-null mice had metastatic myometrial tumors present in the lung, suggesting that LAM tumor cells might in fact originate from the uterus, thus explaining the female sexual dimorphism, the estrogen sensitivity, and the metastatic nature of the LAM tumors.Interestingly, flow cytometry revealed large numbers of granulocytic myeloid derived suppressors cells (G-MDSCs) in the blood and myometrial tumors of uterine-specific Tsc2 null mice. MDSCs are known to accumulate in the setting of chronic inflammation caused by trauma, infection, and various cancers. This granulocytic subtype not only has the capacity to suppress anti-tumor immune cells of the tumor microenvironment, but also directly promotes tumor cell malignant neoplasicity. We found that Tsc2-null myometrial tumors required MDSCs for normal progression, as MDSC depletion or inhibition of MDSC recruitment reduced tumor growth. We have showed that these tumors expressed estrogen receptors and were exquisitely sensitive to estrogen, while other studies demonstrate that G-MDSCs are also positively influenced by estradiol. Therefore, we hypothesized that, in addition to direct effects of estrogen on tumor cells, estrogen also stimulates tumor growth by promoting MDSC production in the bone marrow. We have developed a technique to stimulate MDSC production from mouse bone marrow. Using this strategy, we found that estradiol is indeed a potent promotor of G-MDSC production. These effects occurred in both male and female bone marrow. Employing both pharmacologic agents and bone marrow from ERα; knockout mice, we showed that ERα; is necessary for promoting a G-MDSC fate for immature myeloid cells and precursors. Thus, estradiol may have duel effects in LAM, both directly promoting tumor growth and indirectly upregulating MDSC production, which in turn promotes tumor growth. We propose that these estrogen effects on MDSC production are not limited to LAM and may be important regulators of tumor growth in many tissues.

SAT-141 Glycoprotein NMB (GPNMB) Is Pro-Tumorigenic in TSC2-Null Cancer Cells and Is a Potential Drug Target and Biomarker for Lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis (LAM) is an estrogen-sensitive lung disease found almost exclusively in women that is characterized by hyperproliferation of smooth muscle cells forming small tumors, or LAM lesions throughout the lungs of patients. Growth of these tumors leads to progressive loss of pulmonary function, and sometimes subsequent lung transplantation. LAM tumor cells contain mutations in either the TSC1 or TSC2 genes, leading to activation of the mTORC1 pathway. In fact, mTOR inhibitors such as sirolimus are commonly used to treat LAM; however, these drugs are not always effective and have significant side effects, suggesting the need for new therapeutic targets. Interestingly, another important feature of LAM cells is that they express melanocytic markers that are normally found in melanocytes or melanoma cells. From RNASeq analysis of a mouse model for LAM that we designed, we discovered significant upregulation of the melanocytic marker Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB), a type I transmembrane protein. GPNMB was not only highly expressed in our mouse model (a uterine specific TSC2-null mouse), it was also expressed in TSC2-null cell lines, and human LAM patient lung samples. In our hands, knocking down GPNMB expression by siRNA directed against GPNMB mRNA decreased migration and proliferation in TSC2-null cells. Additionally, we found that GPNMB’s large ectodomain is shed by TSC2-null cells and can be detected in the blood of human patients with LAM. Finally, MMP 2 and 9 can be secreted as a result of ectodomain shedding and its interaction with integrins. Accordingly, we did indeed see a decrease in MMP 2/9 expression in TSC2-null cells with reduced GPNMB expression from treatment with siRNA directed against GPNMB mRNA. Overall, our results demonstrate the potential importance of GPNMB in LAM tumor progression, and suggest that GPNMB may be a possible LAM biomarker and target for its treatment.

Outcomes of lobectomy on pulmonary function for early stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD).

BackgroundLung cancer is the first cause of cancer mortality worldwide. Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. An epidemiological survey discovered that the presence of COPD increases the risk of lung cancer by 4.5‐fold. Lobectomy is considered to be the standard surgical method for early stage non‐small cell lung cancer (NSCLC). However, the influence of lobectomy on the loss of pulmonary function has not been fully investigated in NSCLC patients with COPD.MethodsWe searched the PubMed database using the following strategies: COPD and pulmonary function test (MeSH term) and lobectomy (MeSH term) from 01 January 1990 to 01 January 2019. We selected the articles of patients with COPD. A total of six studies, including 195 patients with COPD, provided lung function values before and after surgery.ResultsFive out of six studies focused on the short‐term change of pulmonary function (within 3–6 months) after lobectomy, and the average loss of FEV1 was 0.11 L (range: −0.33–0.09 L). One study investigated the long‐term change of pulmonary function (within 1–2 years) after lobectomy, and the average loss of FEV1 was 0.15 L (range: −0.29–0.05 L).ConclusionsA short‐term (3–6 months) loss of pulmonary function after operation is acceptable for lung cancer patients with COPD. However, there may be a high risk of postoperative complications in NSCLC patients with COPD. Therefore, surgical treatment needs to be carefully considered for these patients.

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

Mucociliary clearance is an essential airway defense mechanism dependent predominantly on the proper ciliary function and mucus rheology. The crucial role of cilia is evident in `a variety of respiratory diseases, as the ciliary dysfunction is associated with a progressive decline in lung function over time. The activity of cilia is under supervision of multiple physiological regulators, including second messengers. Their role is to enable a movement in coordinated metachronal waves at certain beat frequency. Ciliary function can be modulated by various stimuli, including agents from the group of beta2 agonists, cholinergic drugs, and adenosine triphosphate (ATP). They trigger cilia to move faster in response to elevated cytoplasmic Ca2+ originated from intracellular sources or replenished from extracellular space. Well-known cilia-stimulatory effect of Ca2+ ions can be abolished or even reversed by modulating the phosphodiesterase (PDE)-mediated breakdown of cyclic adenosine monophosphate (cAMP) since the overall change in ciliary beating has been dependent on the balance between Ca2+ ions and cAMP. Moreover, in chronic respiratory diseases, high ATP levels may contribute to cAMP hydrolysis and thus to a decrease in the ciliary beat frequency (CBF). The role of PDE inhibitors in airway cilia-driven transport may help in prevention of progressive loss of pulmonary function often observed despite current therapy. Furthermore, administration of selective PDE inhibitors by inhalation lowers the risk of their systemic effects. Based on this review we may conclude that selective (PDE1, PDE4) or dual PDE inhibitors (PDE3/4) increase the intracellular level of cyclic nucleotides in airway epithelial cells and thus may be an important target in the development of new inhaled mucokinetic agents. Further research is required to provide evidence of their effectiveness and feasibility regarding their cilia-modulating properties.

Quantitative analysis of airway obstruction in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease with progressive pulmonary function loss caused by progressively proliferating LAM cells. The degree of airway obstruction has not been well investigated within the pathogenesis of LAM.Using a combination of ex vivo computed tomography (CT), microCT and histology, the site and nature of airway obstruction in LAM explant lungs was compared with matched control lungs (n=5 each). The total number of airways per generation, total airway counts, terminal bronchioles number and surface density were compared in LAM versus control.Ex vivo CT analysis demonstrated a reduced number of airways from generation 7 on (p<0.0001) in LAM compared with control, whereas whole-lung microCT analysis confirmed the three- to four-fold reduction in the number of airways. Specimen microCT analysis further demonstrated a four-fold decrease in the number of terminal bronchioles (p=0.0079) and a decreased surface density (p=0.0079). Serial microCT and histology images directly showed the loss of functional airways by collapse of airways on the cysts and filling of the airway by exudate.LAM lungs show a three- to four-fold decrease in the number of (small) airways, caused by cystic destruction which is the likely culprit for the progressive loss of pulmonary function.

Molecular epidemiology of Aspergillus species and other moulds in respiratory samples from Argentinean patients with cystic fibrosis.

In cystic fibrosis (CF) patients, fungal colonization of the respiratory tract is frequently found. Aspergillus fumigatus is the most frequently recorded and is associated with loss of pulmonary function and allergic disease (ABPA). The knowledge on prevalence rates of filamentous fungi in CF patients in Latin America is scarce. One hundred and seventy-six fungal isolates recovered from the upper respiratory tract of CF patients from Argentina were identified to species by morphology and DNA sequencing. In total, 90% of CF patients were colonized by Aspergillus sp., followed by Exophiala sp. (14%) and Scedosporium sp. (10%). Among Aspergillus, six species complexes (Fumigati, Flavi, Terrei, Nigri, Usti, and Nidulante) and different cryptospecies were found. Among Scedosporium, three species were observed (Scedosporium apiospermum, Scedosporium aurantiacum and Scedosporium boydii). All Exophiala isolates were identified as Exophiala dermatitidis. Rare filamentous fungi were also found. All cases of ABPA were associated to the presence of A. fumigatus. Mixed colonization with other mould or rare fungi was observed in half of them. To our knowledge, this is the first prospective study of mould species in CF using molecular methods in Latin America. This study shows that Aspergillus sp., E. dermatitidis and Scedosporium sp. have a high frequency in CF patients from Argentina, and by far, A. fumigatus was the most commonly cultured species. Continuous clinical surveillance is required to detect the emergence of new fungal pathogens and to detect resistant or difficult-to-treat species capable of chronic colonizing the airways and of hematogenous dissemination in case of lung transplantation.

Asthma in adults: Principles of treatment.

The goals of treatment are prevention of fatalities, hospitalizations, and emergency department visits, along with achieving good long-term control of asthma, with reduction of symptoms, maintenance of normal activity level, prevention of exacerbations and accelerated loss of pulmonary function (forced expiratory volume in the first second of expiration [FEV1]), and avoidance of harm from therapies. Treatment is often initiated based on the severity of symptoms, physical examination findings, and, for some patients, the FEV1 or peak expiratory flow rates. Comorbidities such as gastroesophageal reflux disease and laryngopharyngeal reflux, rhinitis or rhinosinusitis, sleep apnea, recurrent infections, smoking, and substance abuse should be addressed. Two treatment modalities are indicated only for individuals with allergic asthma: allergen-specific immunotherapy (commonly known as allergy shots), and biologic therapies that target type-2 (T2) inflammation. Allergen immunotherapy is effective in decreasing symptoms and medication use in select patients with mild-to-moderate allergic asthma. In addition, patients who receive allergen immunotherapy for allergic rhinitis may have a decreased risk of developing asthma. Omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab are monoclonal antibodies that target T2 inflammation and are indicated for either moderate-to-severe or severe asthma. These have been well studied to improve asthma symptoms and have specific characteristics unique to each individual medication. A focus on adherence can be considered in choosing therapy because it is not clear which biologic to choose in T2 high asthma at this time.

Cross-Sectional Study on the Association between Pulmonary Function and Sarcopenia in Brazilian Community-Dwelling Elderly from the Amazon Region.

To compare the obtained and expected values of pulmonary function variables between sarcopenic and non-sarcopenic elderly; verify the association between the pulmonary function and the indicators and diagnosis of sarcopenia; and establish cut-off points for pulmonary function variables to predict sarcopenia. Cross-sectional study. Macapá, Brazil. community-dwelling elderly ≥ 60 years old (n=383), both sexes. Were evaluated according to variables of pulmonary function (spirometry) and sarcopenia, according to the EWGSOP consensus. The association between pulmonary function and sarcopenia was performed using logistic regression and cut-off points established from the ROC Curve. The prevalence of sarcopenia was 12.53% (n = 48). Sarcopenic individuals had significantly lower mean values for FVC, FEV1, FEF25-75% and PEF than non-sarcopenic. After adjustment, spirometric variables were inversely associated with sarcopenia (the increase by one unit of liter in FVC, FEV1 and FEF25-75% decreased the probability of sarcopenia by 59%, 67% and 39%, respectively), and the majority of these variables with the muscular strength indicator. Cut-off points, for elderly men and women, were discriminant criteria for the presence of sarcopenia: FVC (≤2.52 L and ≤1.82 L), FEV1 (≤2.1 L and ≤1.39 L), PEF (≤3.45 L/s and ≤2.93 L/s) and FEF5-75% (≤1.97 L/s and ≤1.74 L/s). There was loss of pulmonary function in sarcopenic elderly patients and an inverse association with the diagnosis of sarcopenia and its indicators. Cut-off points of pulmonary function variables can be used as a useful tool to discriminate sarcopenia.

The Association Between Vitamin D Status and Pulmonary Function in Pediatric Patients With Cystic Fibrosis

Sufficient vitamin D levels play an essential role in bone health and, more recently, in pulmonary function. Achieving sufficient vitamin D levels is challenging, especially among individuals with malabsorptive diseases, such as cystic fibrosis (CF). Cystic fibrosis is characterized by a progressive loss of pulmonary function and fat malabsorption, increasing the risk for vitamin D deficiency. After reviewing the literature for pediatric patients with CF, the association between vitamin D status and pulmonary function remains unclear. More studies are needed to evaluate whether adequate vitamin D status can assist in maintaining pulmonary function and slowing disease progression.

Outcomes of scapulothoracic fusion in facioscapulohumeral muscular dystrophy: A systematic review.

Facioscapulohumeral muscular dystrophy (FSHD) is a rare condition associated with selective weakness of the muscles of the upper arm, face, and shoulder girdle, negatively affecting daily activities. Scapulothoracic arthrodesis may restore shoulder function and improve quality of life. The purpose of this review is to evaluate the outcomes and complications of scapulothoracic arthrodesis in FSHD patients. Medline, Pubmed, and Embase were systematically searched. Studies were included if they described scapulothoracic arthrodesis in FSHD with follow-up, and outcomes were adequately reported. Thirteen eligible articles reported the outcomes of 199 arthrodesis in 130 patients. The mean gain of shoulder forward elevation and abduction were 45° (p < 0.05) and 40° (p < 0.05), respectively. There was an overall cosmetic satisfaction and improved performance of daily activities. There is limited and heterogeneous data on changes in pulmonary function, but such changes are clinically insignificant. The rate of complications was 41% of which 10% were serious, requiring an intervention or re-admission. The most common complications were hardware failure (8%), non-union (6%), and pneumothorax (5%). Scapulothoracic arthrodesis improved cosmesis, performance of daily activities and shoulder motion with no clinically significant loss of pulmonary function. The complication rate is high, and some are potentially serious.

FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury.

SummaryIdiopathic pulmonary fibrosis is a common form of interstitial lung disease resulting in alveolar remodeling and progressive loss of pulmonary function because of chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures expressing atypical proximal airway epithelial markers replace alveolar structures, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Bronchial epithelial stem cells (BESCs) can give rise to AT2 and AT1 cells or honeycomb cysts following bleomycin-mediated lung injury. However, little is known about what controls this binary decision or whether this decision can be reversed. Here we report that inactivation of Fgfr2b in BESCs impairs their contribution to both alveolar epithelial regeneration and honeycomb cysts after bleomycin injury. By contrast overexpression of Fgf10 in BESCs enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts.

Wash-in/wash-out phase xenon-enhanced area-detector CT (ADCT): utility for regional ventilation, pulmonary functional loss and clinical stage evaluations of smokers

BackgroundXenon (Xe)-enhanced area-detector computed tomography (ADCT) can visualize regional distribution of Xe within the lungs and demonstrate regional ventilation differences in smokers and pat...

OR34-5 Infiltrating Neutrophils and Neutrophil Elastase (NE) Promote Tumor Growth in a Mouse Model for Lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis (LAM) is a rare disease occurring almost exclusively in women whereby metastatic smooth-muscle cell-like adenomas grow within the lungs, resulting in loss of pulmonary function. LAM cells contain mutations in tuberous sclerosis 1 or 2 genes (TSC1 or TSC2), which leads to heightened mammalian target of rapamycin complex1 (mTORC1) activity and cell proliferation. The LAM cell origin remains unknown; however, we reported that inactivation of the Tsc2 gene in the mouse uterus resulted in myometrial tumors with nearly all known features of LAM, including over-expression of melanocytic markers that are pathognomonic of LAM tumor cells. Approximately 50% of animals developed metastatic myometrial tumors in the lung, suggesting that LAM cells might originate from the uterine myometrium, possibly explaining its overwhelming female prevalence. Estrogen ablation by oophorectomy or aromatase inhibition resulted in nearly complete regression of Tsc2-null myometrial tumors, indicating that, even without TSC2, estradiol is required to maintain tumors. Through RNAseq analysis of genes that are both estrogen and Tsc2 mediated, we identified the serine protease Neutrophil Elastase (NE) as being highly expressed in Tsc2-null uterine tumors. NE is expressed in and secreted by granulocytic neutrophils and myeloid-derived suppressor cells (MDSCs), both of which are known to be upregulated in the blood and stroma of various cancers such as breast, lung, melanoma, and prostate. NE is thought to promote pro-tumorigenic phenotypes such as proliferation, EMT, migration, invasion, and ultimately metastasis. We hypothesize that NE from infiltrating MDSCs promotes LAM tumor progression. Using flow cytometry as well as immunofluorescence, we show increased numbers of MDSCs in the blood, uterus and lungs of Tsc2-null KO mice. Immunodepleting MDSCs results in reduced tumor growth and myometrial thickness, as does blockade of MDSC recruitment to tumors using a CXCR2 antagonist. Interestingly, treatment with the NE inhibitor sivelestat phenocopies the results from MDSC depletion, leading to reduced MDSC accumulation in the tumor site, reduced tumor growth, and less myometrial thickening. Finally, using TSC2-null cell lines, we find that NE promotes aggressive tumor cell behaviors such as migration and proliferation. Thus, our data highlights the importance of MDSCs and their product NE in LAM progression, and identifies novel molecular mediators of LAM tumor growth and invasion.

Radiological progression and lung function decrements among silica-exposed ceramic workers: a longitudinal study

Objectives: This follow-up study set out to evaluate the natural course and radiographic progression of silicosis among ceramic workers and describe the risk factors related with disease progression. Materials and methods: We retrospectively analyzed the data of ceramic workers with silicosis who were referred to our hospital between February 2010 and March 2018. A total of 165 ceramic workers followed at least 24 months and with at least two chest radiographs were included in the study. Results: The duration of silica exposure ranged from 5.5 to 27 (median 13.6) years. The numbers of patients according to follow-up time were as follows: 38 (2–2.9) years, 77 (3–3.9) years, 26 (4–4.9) years, 17 (5–5.9) years, and 7 (≥6) years. Overall 62 of 165 (37.5%) cases showed radiologic evidences of progression ranging from 2 to 8.9 years (mean 3.7 years). Pulmonary function loss rate among silicosis patients was 36.9% (61/165). Multiple logistic regression analysis showed a significant relation between radiographic progression and age (OR, 1.079: 95% CI, 1.011–1.152), follow-up time (OR, 1.557: 95% CI, 1.144–2.118), and the ILO category (category 2 or 3) at first visit (OR, 3.507: 95% CI, 1.505–8.170). Conclusions: Our findings suggest that one-third of Turkish ceramic workers with silicosis who were followed up to 8.9 years showed progression that was related to increasing age greater ILO category at time of initial visit and follow-up duration.

Polydatin ameliorates pulmonary fibrosis by suppressing inflammation and the epithelial mesenchymal transition via inhibiting the TGF-β/Smad signaling pathway.

Pulmonary fibrosis is a chronic and progressive lung disease which results in a loss of pulmonary function and eventually respiratory failure. Inflammation and epithelial mesenchymal transition (EMT) play important roles in the pathogenesis of pulmonary fibrosis. This study aimed to investigate the therapeutic effect of polydatin (PD) in bleomycin-induced pulmonary fibrosis. A bleomycin-induced pulmonary fibrosis animal model used SD rats. Morphological changes were analyzed by hematoxylin-eosin staining. RT-qPCR and western blot were used for the detection of the expression of TGF-β1, collagen I, collagen III, E-cadherin, fibronectin and the ratios of p-Smad2/Smad2, p-Smad3/Smad3. The concentrations of PICP, PIIINP, TNF-α, IL-1β, IL-6 and IL-17 were measured by enzyme linked immunosorbent assay (Elisa) assay. Results showed that PD attenuated bleomycin-induced pulmonary fibrosis. The beneficial effect of PD was possibly related to the inhibition of inflammation and EMT through suppressing the TGF-β/Smad signaling pathway. Our findings suggested that PD might be a potential therapeutic candidate in the treatment of pulmonary fibrosis.

Dysregulated Calcium Homeostasis in Cystic Fibrosis Neutrophils Leads to Deficient Antimicrobial Responses.

Cystic fibrosis (CF), one of the most common human genetic diseases worldwide, is caused by a defect in the CF transmembrane conductance regulator (CFTR). Patients with CF are highly susceptible to infections caused by opportunistic pathogens (including Burkholderia cenocepacia), which induce excessive lung inflammation and lead to the eventual loss of pulmonary function. Abundant neutrophil recruitment into the lung is a key characteristic of bacterial infections in CF patients. In response to infection, inflammatory neutrophils release reactive oxygen species and toxic proteins, leading to aggravated lung tissue damage in patients with CF. The present study shows a defect in reactive oxygen species production by mouse Cftr-/- , human F508del-CFTR, and CF neutrophils; this results in reduced antimicrobial activity against B. cenocepacia Furthermore, dysregulated Ca2+ homeostasis led to increased intracellular concentrations of Ca2+ that correlated with significantly diminished NADPH oxidase response and impaired secretion of neutrophil extracellular traps in human CF neutrophils. Functionally deficient human CF neutrophils recovered their antimicrobial killing capacity following treatment with pharmacological inhibitors of Ca2+ channels and CFTR channel potentiators. Our findings suggest that regulation of neutrophil Ca2+ homeostasis (via CFTR potentiation or by the regulation of Ca2+ channels) can be used as a new therapeutic approach for reestablishing immune function in patients with CF.

Fructose-1,6-Bisphosphate Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice and Inhibits the Proliferation of Lung Fibroblasts

Pulmonary fibrosis is a specific form of interstitial pneumonia. In addition to the idiopathic cause, it may be caused by drugs such as bleomycin (BLM)-used in the treatment of tumors. Fructose-1,6-bisphosphate (FBP) is a high-energy endogenous glycolytic compound that has antifibrotic, anti-inflammatory, and immunomodulatory effects. The aim of this study was to investigate the effects of FBP on both BLM-induced pulmonary fibrosis in mice and in a human embryonic lung fibroblast (MRC-5) culture system. C57BL/6 mice were divided into four groups: control, FBP, BLM, and BLM plus FBP. A single dose of bleomycin (7.5U/kg) was administered intratracheally, and survival, body weight, Ashcroft score, and histological analysis were evaluated. Pulmonary function and bronchoalveolar lavage fluid (BALF) were also evaluated after a single dose of bleomycin (1.2U/kg-intratracheally). Treatment with FBP (500mg/kg) was given on day 0 intraperitoneally. Fibroblasts (MRC-5 cells) were used to access the effect of FBP in vitro. In vivo, FBP increased the survival rate and reduced body weight loss (BLM vs. BLM plus FBP-p< 0.05). FBP also prevented BLM-induced loss of pulmonary function and decreased BALF inflammatory cells, level of fibrosis, and superficial collagen density (p< 0.05). In vitro, FBP (0.62 and 1.25mM) had inhibitory activity on MRC-5 cells and was able to induce senescence in fibroblasts. These results showed that FBP has the potential of reducing the toxic effects of BLM and may provide supportive therapy for conventional methods used for the treatment of cancer.