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Gert Folkerts - One of the best experts on this subject based on the ideXlab platform.
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Non-digestible oligosaccharides partially prevent the development of LPS-induced Lung Emphysema in mice
PharmaNutrition, 2019Co-Authors: Hamed Janbazacyabar, Gert Folkerts, Jeroen Van Bergenhenegouwen, Kim A.t. Verheijden, Thea Leusink-muis, Ardy Van Helvoort, Johan Garssen, Saskia BraberAbstract:Abstract Chronic obstructive pulmonary disease (COPD), a progressive inflammatory disorder, is also known as a systemic inflammatory disease, in which the gut-Lung interaction plays an important role. The use of non-digestible oligosaccharides (NDOs) has gained attention in airway diseases due to their systemic effects on inflammatory markers. Here, the preventive effects of specific non-digestible oligosaccharides (GOS/lcFOS/lvPectin) were investigated in a murine lipopolysaccharide (LPS)-induced Emphysema model. Nasal LPS-installations were used to induce Emphysema in male BALB/c mice. Two weeks prior to the first LPS challenge, mice received GOS/lcFOS/lvPectin (9:1:2) mixture by gavage (25 mg NDOs/200 μl PBS) five days a week until day 28. The LPS-induced neutrophil influx in bronchoalveolar lavage fluid (BALF) decreased by >60% after intervention with GOS/lcFOS/lvPectin and the development of Lung Emphysema, measured by mean linear intercept, was prevented. Macroscopic examination of heart tissue revealed that GOS/lcFOS/lvPectin pretreatment attenuated the LPS-induced increase in right ventricular heart hypertrophy. In summary, GOS/lcFOS/lvPectin prevented characteristic features of COPD in the LPS-induced Lung Emphysema model. Since no therapy is available to stop or prevent development of COPD, oligosaccharides may have potential to be used as stand alone or in combination with other anti-inflammatory nutrients or drugs to diminish disease progression in COPD.
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Humic acid enhances cigarette smoke-induced Lung Emphysema in mice and IL-8 release of human monocytes
Pulmonary pharmacology & therapeutics, 2011Co-Authors: Sven Van Eijl, Esmaeil Mortaz, Frans P Nijkamp, Gert Folkerts, Ana F. Ferreira, Frieke Kuper, Nanne BloksmaAbstract:Tobacco smoke is the main factor in the etiology of Lung Emphysema. Generally prolonged, substantial exposure is required to develop the disease. Humic acid is a major component of cigarette smoke that accumulates in smokers' Lungs over time and induces tissue damage. Objectives: To investigate whether humic acid pre-loading potentiates the development of cigarette smoke-induced Lung Emphysema in mice and increases IL-8 release by human monocytes. Methods: C57BL/6J mice received humic acid or aqueous vehicle by tracheal installation on day 0 and day 7. From day 21 to day 84, the mice were exposed to cigarette smoke or clean air for 5 days/week. Twenty-four hours after the last exposure we determined leukocytes in Lung lavage, heart hypertrophy and alveolar wall destruction. Human monocytes were incubated with cigarette smoke extract (CSE), humic acid or the combination overnight. Results: Humic acid nor cigarette smoke caused alveolar wall destruction within two months. Interestingly, the combination did induce Lung Emphysema. Humic acid, cigarette smoke or the combination did not change leukocyte types and numbers in Lung lavage fluid, but the combination caused peribronchiolar and perivascular lymphocyte infiltration. Humic acid treatment resulted in a high proportion of alveolar macrophages heavily loaded with intracellular granula. Humic acid also induces the release of IL-8 from human monocytes and enhances the CSE-induced IL-8 release. Conclusions: Humic acid deposition in the Lungs potentiates the development of cigarette smoke-induced interstitial inflammation and Lung Emphysema. Moreover, humic acid promotes IL-8 release from human monocytes. Since humic acid accumulates steadily in the Lungs of smokers, this may provide an explanation for the natural history on late onset of this disease. The model described here offers a novel way to study Emphysema and may direct the search for new therapeutic approaches. © 2011 Elsevier Ltd.
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A low vitamin A status increases the susceptibility to cigarette smoke-induced Lung Emphysema in C57BL/6J mice.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2011Co-Authors: S. Van Eijl, Esmaeil Mortaz, Frans P Nijkamp, Gert Folkerts, Cees Versluis, Nanne BloksmaAbstract:Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered a major player in the pathogenesis of COPD. The inflamed airways of COPD patients contain several inflammatory cells. Vitamin A metabolites have been implicated in the repair of Lung damage. Exposure to cigarette smoke has been shown to depress levels of retinol in Lungs of rats. The purpose of this study was to investigate if a low, but not deficient, vitamin A status potentiated susceptibility to the development of cigarette smoke-induced Lung Emphysema in mice. Mice were bred that were the offspring’s of 3 generations of mice that were fed a purified diet containing low levels of vitamin A and exposed to cigarette smoke for 3 months, every weekday. Then, levels of 9-cis, 13-cis, and all-trans retinoic acid, retinol and retinyl palmitate were measured in plasma, liver and right Lung lobe. The left Lung lobe was used to assess mean linear intercept (Lm), as a measure of smoke-induced Lung damage. Average feed intakes were not different between treatment groups. We show that both retinol and retinyl palmitate levels were dramatically decreased in the storage organs of mice on the low vitamin A diet (retinol 2-fold in both Lung and liver, and retinyl palmitate 5- fold in Lung) which shows that the depletion was successful. However, this treatment did not result in the development of Lung Emphysema. However, smoke exposure led to a significant increase in Lm in mice with a low vitamin A status compared to the room air-breathing controls. Lung levels of acid retinoids were similar in all mice, irrespective of diet or smoke exposure. Concluding, a low vitamin A status increases the susceptibility to the development of cigarette smoke-induced Lung Emphysema, possibly because of decreased anti-oxidant capacity in the Lungs due to locally reduced retinol and retinyl palmitate levels. These observations indicate that human populations with a low vitamin A status and a high prevalence of smoking may be at increased risk of developing Lung Emphysema.
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Cigarette smoke-induced Lung Emphysema in mice is associated with prolyl endopeptidase, an enzyme involved in collagen breakdown
American journal of physiology. Lung cellular and molecular physiology, 2010Co-Authors: Saskia Braber, Frans P Nijkamp, J. Edwin Blalock, Johan Garssen, Pim J. Koelink, Paul A.j. Henricks, Patricia L. Jackson, Aletta D. Kraneveld, Gert FolkertsAbstract:There is increasing evidence that the neutrophil chemoattractant proline-glycine-proline (PGP), derived from the breakdown of the extracellular matrix, plays an important role in neutrophil recruitment to the Lung. PGP formation is a multistep process involving neutrophils, metalloproteinases (MMPs), and prolyl endopeptidase (PE). This cascade of events is now investigated in the development of Lung Emphysema. A/J mice were whole body exposed to cigarette smoke for 20 wk. After 20 wk or 8 wk after smoking cessation, animals were killed, and bronchoalveolar lavage fluid and Lung tissue were collected to analyze the neutrophilic airway inflammation, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels. Lung tissue degradation was assessed by measuring the mean linear intercept. Additionally, we investigated the effect of the peptide l-arginine-threonine-arginine (RTR), which binds to PGP sequences, on the smoke-induced neutrophil influx in the Lung after 5 days of smoke exposure. Neutrophilic airway inflammation was induced by cigarette smoke exposure. MMP-8 and MMP-9 levels, PE activity, and PGP levels were elevated in the Lungs of cigarette smoke-exposed mice. PE was highly expressed in epithelial and inflammatory cells (macrophages and neutrophils) in Lung tissue of cigarette smoke-exposed mice. After smoking cessation, the neutrophil influx, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels were decreased or reduced to normal levels. Moreover, RTR inhibited the smoke-induced neutrophil influx in the Lung after 5 days' smoke exposure. In the present murine model of cigarette smoke-induced Lung Emphysema, it is demonstrated for the first time that all relevant components (neutrophils, MMP-8, MMP-9, PE) involved in PGP formation from collagen are upregulated in the airways. Together with MMPs, PE may play an important role in the formation of PGP and thus in the pathophysiology of Lung Emphysema.
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A comparison of fixation methods on Lung morphology in a murine model of Emphysema
American journal of physiology. Lung cellular and molecular physiology, 2010Co-Authors: Saskia Braber, Kim A.t. Verheijden, Paul A.j. Henricks, Aletta D. Kraneveld, Gert FolkertsAbstract:Emphysema is characterized by enlargement of the alveoli, which is the most important parameter to assess the presence and severity of this disease. Alveolar enlargement is primarily defined on morphological criteria; therefore, characterization of this disease with morphological parameters is a prerequisite to study the pathogenesis. For this purpose, different methods of Lung fixation were evaluated in a murine model of LPS-induced Lung Emphysema. Five different methods of Lung fixation were evaluated: intratracheal instillation of fixatives, in situ fixation, fixed-volume fixation, vascular whole body perfusion, and vacuum inflation. In addition, the effects of three different fixatives (10% formalin, Carnoy's, and agarose/10% formalin solution) and two embedding methods (paraffin and plastic) were investigated on the murine Lung morphology. Mice received intranasal administration of LPS to induce alveolar wall destruction. Quantification of air space enlargement was determined by mean linear intercept analysis, and the histological sections were analyzed for the most optimal fixation method. Additionally, routine immunohistological staining was performed on Lung tissue of PBS-treated mice. Intratracheal instillation of formalin or agarose/formalin solution, in situ fixation, and fixed-volume fixation provided a normal Lung architecture, in contrast to the Lungs fixed via whole body perfusion and vacuum inflation. Formalin-fixed Lungs resulted in the most optimal Lung morphology for Lung Emphysema analysis when embedded in paraffin, while for Carnoy's fixed Lungs, plastic embedding was preferred. The histological findings, the mean linear intercept measurement, and the immunohistochemistry data demonstrated that fixation by intratracheal instillation of 10% formalin or in situ fixation with 10% formalin are the two most optimal methods to fix Lungs for alveolar enlargement analysis to study Lung Emphysema.
Frans P Nijkamp - One of the best experts on this subject based on the ideXlab platform.
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Humic acid enhances cigarette smoke-induced Lung Emphysema in mice and IL-8 release of human monocytes
Pulmonary pharmacology & therapeutics, 2011Co-Authors: Sven Van Eijl, Esmaeil Mortaz, Frans P Nijkamp, Gert Folkerts, Ana F. Ferreira, Frieke Kuper, Nanne BloksmaAbstract:Tobacco smoke is the main factor in the etiology of Lung Emphysema. Generally prolonged, substantial exposure is required to develop the disease. Humic acid is a major component of cigarette smoke that accumulates in smokers' Lungs over time and induces tissue damage. Objectives: To investigate whether humic acid pre-loading potentiates the development of cigarette smoke-induced Lung Emphysema in mice and increases IL-8 release by human monocytes. Methods: C57BL/6J mice received humic acid or aqueous vehicle by tracheal installation on day 0 and day 7. From day 21 to day 84, the mice were exposed to cigarette smoke or clean air for 5 days/week. Twenty-four hours after the last exposure we determined leukocytes in Lung lavage, heart hypertrophy and alveolar wall destruction. Human monocytes were incubated with cigarette smoke extract (CSE), humic acid or the combination overnight. Results: Humic acid nor cigarette smoke caused alveolar wall destruction within two months. Interestingly, the combination did induce Lung Emphysema. Humic acid, cigarette smoke or the combination did not change leukocyte types and numbers in Lung lavage fluid, but the combination caused peribronchiolar and perivascular lymphocyte infiltration. Humic acid treatment resulted in a high proportion of alveolar macrophages heavily loaded with intracellular granula. Humic acid also induces the release of IL-8 from human monocytes and enhances the CSE-induced IL-8 release. Conclusions: Humic acid deposition in the Lungs potentiates the development of cigarette smoke-induced interstitial inflammation and Lung Emphysema. Moreover, humic acid promotes IL-8 release from human monocytes. Since humic acid accumulates steadily in the Lungs of smokers, this may provide an explanation for the natural history on late onset of this disease. The model described here offers a novel way to study Emphysema and may direct the search for new therapeutic approaches. © 2011 Elsevier Ltd.
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A low vitamin A status increases the susceptibility to cigarette smoke-induced Lung Emphysema in C57BL/6J mice.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2011Co-Authors: S. Van Eijl, Esmaeil Mortaz, Frans P Nijkamp, Gert Folkerts, Cees Versluis, Nanne BloksmaAbstract:Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered a major player in the pathogenesis of COPD. The inflamed airways of COPD patients contain several inflammatory cells. Vitamin A metabolites have been implicated in the repair of Lung damage. Exposure to cigarette smoke has been shown to depress levels of retinol in Lungs of rats. The purpose of this study was to investigate if a low, but not deficient, vitamin A status potentiated susceptibility to the development of cigarette smoke-induced Lung Emphysema in mice. Mice were bred that were the offspring’s of 3 generations of mice that were fed a purified diet containing low levels of vitamin A and exposed to cigarette smoke for 3 months, every weekday. Then, levels of 9-cis, 13-cis, and all-trans retinoic acid, retinol and retinyl palmitate were measured in plasma, liver and right Lung lobe. The left Lung lobe was used to assess mean linear intercept (Lm), as a measure of smoke-induced Lung damage. Average feed intakes were not different between treatment groups. We show that both retinol and retinyl palmitate levels were dramatically decreased in the storage organs of mice on the low vitamin A diet (retinol 2-fold in both Lung and liver, and retinyl palmitate 5- fold in Lung) which shows that the depletion was successful. However, this treatment did not result in the development of Lung Emphysema. However, smoke exposure led to a significant increase in Lm in mice with a low vitamin A status compared to the room air-breathing controls. Lung levels of acid retinoids were similar in all mice, irrespective of diet or smoke exposure. Concluding, a low vitamin A status increases the susceptibility to the development of cigarette smoke-induced Lung Emphysema, possibly because of decreased anti-oxidant capacity in the Lungs due to locally reduced retinol and retinyl palmitate levels. These observations indicate that human populations with a low vitamin A status and a high prevalence of smoking may be at increased risk of developing Lung Emphysema.
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Cigarette smoke-induced Lung Emphysema in mice is associated with prolyl endopeptidase, an enzyme involved in collagen breakdown
American journal of physiology. Lung cellular and molecular physiology, 2010Co-Authors: Saskia Braber, Frans P Nijkamp, J. Edwin Blalock, Johan Garssen, Pim J. Koelink, Paul A.j. Henricks, Patricia L. Jackson, Aletta D. Kraneveld, Gert FolkertsAbstract:There is increasing evidence that the neutrophil chemoattractant proline-glycine-proline (PGP), derived from the breakdown of the extracellular matrix, plays an important role in neutrophil recruitment to the Lung. PGP formation is a multistep process involving neutrophils, metalloproteinases (MMPs), and prolyl endopeptidase (PE). This cascade of events is now investigated in the development of Lung Emphysema. A/J mice were whole body exposed to cigarette smoke for 20 wk. After 20 wk or 8 wk after smoking cessation, animals were killed, and bronchoalveolar lavage fluid and Lung tissue were collected to analyze the neutrophilic airway inflammation, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels. Lung tissue degradation was assessed by measuring the mean linear intercept. Additionally, we investigated the effect of the peptide l-arginine-threonine-arginine (RTR), which binds to PGP sequences, on the smoke-induced neutrophil influx in the Lung after 5 days of smoke exposure. Neutrophilic airway inflammation was induced by cigarette smoke exposure. MMP-8 and MMP-9 levels, PE activity, and PGP levels were elevated in the Lungs of cigarette smoke-exposed mice. PE was highly expressed in epithelial and inflammatory cells (macrophages and neutrophils) in Lung tissue of cigarette smoke-exposed mice. After smoking cessation, the neutrophil influx, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels were decreased or reduced to normal levels. Moreover, RTR inhibited the smoke-induced neutrophil influx in the Lung after 5 days' smoke exposure. In the present murine model of cigarette smoke-induced Lung Emphysema, it is demonstrated for the first time that all relevant components (neutrophils, MMP-8, MMP-9, PE) involved in PGP formation from collagen are upregulated in the airways. Together with MMPs, PE may play an important role in the formation of PGP and thus in the pathophysiology of Lung Emphysema.
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Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation.
Respiratory research, 2010Co-Authors: Saskia Braber, Frans P Nijkamp, Paul A.j. Henricks, Aletta D. Kraneveld, Gert FolkertsAbstract:Tobacco smoking irritates and damages the respiratory tract and contributes to a higher risk of developing Lung Emphysema. At present, smoking cessation is the only effective treatment for reducing the progression of Lung Emphysema, however, there is hardly anything known about the effects of smoking cessation on cytokine and chemokine levels in the airways. To the best of our knowledge, this is the first reported in vivo study in which cytokine profiles were determined after cessation of cigarette smoke exposure. The severity of airway remodeling and inflammation was studied by analyzing alveolar enlargement, heart hypertrophy, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and Lung tissue and by determining the cytokine and chemokine profiles in the BALF of A/J mice exposed to cigarette smoke for 20 weeks and 8 weeks after smoking cessation. The alveolar enlargement and right ventricle heart hypertrophy found in smoke-exposed mice remained unchanged after smoking cessation. Although the neutrophilic inflammation in the BALF of cigarette smoke-exposed animals was reduced after smoking cessation, a sustained inflammation in the Lung tissue was observed. The elevated cytokine (IL-1α and TNF-α) and chemokine (CCL2 and CCL3) levels in the BALF of smoke-exposed mice returned to basal levels after smoking cessation, while the increased IL-12 levels did not return to its basal level. The cigarette smoke-enhanced VEGF levels did not significantly change after smoking cessation. Moreover, IL-10 levels were reduced in the BALF of smoke-exposed mice and these levels were still significantly decreased after smoking cessation compared to the control animals. The inflammatory changes in the airways caused by cigarette smoke exposure were only partially reversed after smoking cessation. Although smoking cessation should be the first step in reducing the progression of Lung Emphysema, additional medication could be provided to tackle the sustained airway inflammation.
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ATP in the pathogenesis of Lung Emphysema.
European journal of pharmacology, 2009Co-Authors: Esmaeil Mortaz, Saskia Braber, Maiwand Nazary, Masoumh Ezzati Givi, Frans P Nijkamp, Gert FolkertsAbstract:Extracellular ATP is a signaling molecule that often serves as a danger signal to alert the immune system of tissue damage. This molecule activates P2 nucleotide receptors, that include the ionotropic P2X receptors and metabotropic P2Y receptors. Recently, it has been reported that ATP accumulates in the airways of both asthmatic patients and sensitized mice after allergen challenge. The role and function of ATP in the pathogenesis of chronic obstructive pulmonary diseases (COPD) are not well understood. In this study we investigated the effect of cigarette smoke on purinergic receptors and ATP release by neutrophils. Neutrophils and their mediators are key players in the pathogenesis of Lung Emphysema. Here we demonstrated that in an in vivo model of cigarette smoke-induced Lung Emphysema, the amount of ATP was increased in the bronchoalveolar lavage fluid. Moreover, activation of neutrophils with cigarette smoke extract induced ATP release. Treatment of neutrophils with apyrase (catalyses the hydrolysis of ATP to yield AMP) and suramin (P2-receptor antagonist) abrogated the release of CXCL8 and elastase induced by cigarette smoke extract and exogenous ATP. These observations indicate that activation of purinergic signaling by cigarette smoke may take part in the pathogenesis of Lung Emphysema.
Marius Horger - One of the best experts on this subject based on the ideXlab platform.
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Impact of endobronchial coiling on segmental bronchial lumen in treated and untreated Lung lobes: Correlation with changes in Lung volume, clinical and pulmonary function tests
European radiology, 2015Co-Authors: Christopher Kloth, Wolfgang M. Thaiss, Jürgen Hetzel, Hendrik Ditt, Ulrich Grosse, Konstantin Nikolaou, Marius HorgerAbstract:Objectives To assess the impact of endobronchial coiling on the segment bronchus cross-sectional area and volumes in patients with Lung Emphysema using quantitative chest-CT measurements.
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incidental Lung volume reduction following fulminant pulmonary hemorrhage in a patient with severe Emphysema
Lung, 2015Co-Authors: Juergen Hetzel, Werner Spengler, Marius Horger, Michael BoeckelerAbstract:Endoscopic Lung volume reduction is an emerging technique meant to improve Lung function parameters, quality of life, and exercise tolerance in patients with severe Lung Emphysema. This is the first report of Lung volume reduction by autologous blood in a patient with non-bullous Lung Emphysema. A 74-year-old woman with heterogeneous Lung Emphysema developed accidentally diffuse lobar bleeding immediately after valve placement. Due to persistent hemorrhage, the valves had to be removed shortly thereafter. Despite extraction of the valves, respiratory function of the patient improved rapidly indicated also by a drop in the COPD assessment test questionnaire, 3 months later. This was consistent with both improvement of Lung function tests and six-minute walking test.
A. Valipour - One of the best experts on this subject based on the ideXlab platform.
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Effectiveness and efficacy of minimally invasive Lung volume reduction surgery for Emphysema.
GMS health technology assessment, 2014Co-Authors: Daniela Pertl, Alexander Eisenmann, Ulrike Holzer, Anna-theresa Renner, A. ValipourAbstract:Lung Emphysema is a chronic, progressive and irreversible destruction of the Lung tissue. Besides non-medical therapies and the well established medical treatment there are surgical and minimally invasive methods for Lung volume reduction (LVR) to treat severe Emphysema. This report deals with the effectiveness and cost-effectiveness of minimally invasive methods compared to other treatments for LVR in patients with Lung Emphysema. Furthermore, legal and ethical aspects are discussed. No clear benefit of minimally invasive methods compared to surgical methods can be demonstrated based on the identified and included evidence. In order to assess the different methods for LVR regarding their relative effectiveness and safety in patients with Lung Emphysema direct comparative studies are necessary.
Elizabeth J Silverstone - One of the best experts on this subject based on the ideXlab platform.
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Quantitative CT scanning using a Lung Emphysema software package in familial Birt-Hogg-Dubé syndrome
European Respiratory Journal, 2014Co-Authors: Sameh Samuel, Deborah H. Yates, Jonathan Lee, Kathy Tucker, Elizabeth J SilverstoneAbstract:Background: Birt-Hogg- Dube syndrome (BHD) is a rare autosomal dominant disorder associated with skin lesions, cystic Lung disease and renal tumours. Quantification of Lung cysts volume can be performed using a Lung Emphysema software package, but correlation with Lung function has not been previously examined. Aim: We aimed to correlate total Lung Emphysema volume with total Lung capacity (TLC) in 6 patients with BHD. Method: Retrospective review of clinically gathered data, CT Emphysema volume (using Philips Brilliance Emphysema Software), and Lung function (using body plethysmography Sensormedics Vmax Encore Vision). Results: The use of Quantitative CT (QCT) Emphysema package correlated with plethysmographic total Lung capacity (TLC) [correlation coefficient 0.42] but FEV1/FVC did not seem to correlate with Emphysema ratio [correlation coefficient -0.19]. Conclusion: There is evidence of correlation between TLC and QCT Lung volumes in Birt-Hogg-Dube syndrome. Quantitative CT scanning requires further evaluation in this condition. Key Words Birt-Hogg-Dube Syndrome, Quantitative CT, Lung Function, Pneumothroax.
