tbuckley/cabot-search huggingface dataset:
Tissue inhibitor of metalloproteinases-;2 gene polymorphisms in chronic obstructive pulmonary disease
Authors: K. Hirano, T. Sakamoto, Y. Uchida, Y. Morishima, K. Masuyama, Y. Ishii, A. Nomura, M. Ohtsuka, K. Sekizawa
Journal: European Respiratory Journal (2001)

Proteinase/antiproteinase imbalance is the most widely accepted theory for development of chronic obstructive pulmonary disease (COPD). Mutations of tissue inhibitor of metalloproteinases-;2 (TIMP-;2) that downregulate its activity may increase the activities of matrix metalloproteinases and result in the degradation of the lung matrix. Polymorphisms of the TIMP-;2 gene were investigated in 88 COPD patients and 40 control subjects. The variations were examined by single-strand conformational polymorphism analysis followed by sequencing. Two polymorphisms were identified, +853 G/A and −418 G/C nucleotide substitutions. There was a significant deviation in the genotypic frequencies at +853 and the allele frequencies for G were significantly higher in the COPD patient group than in the control group. For locus −418, the allele frequencies for C in the COPD patient group also tended to be higher than those in the control group. The +853 G/A nucleotide substitution was a silent variant. The −418 G/C substitution was located in the consensus sequence for the Sp1 binding site. These polymorphisms may be associated with the development of chronic obstructive pulmonary disease, decreasing the transcription and stability of the messenger ribonucleic acid, and available as genetic markers of susceptibility to the disease.
Pulmonary toxicity with mefloquine
Authors: E. Udry, F. Bailly, M. Dusmet, P. Schnyder, R. Lemoine, J.W. Fitting
Journal: European Respiratory Journal (2001)

This report presents a case of acute lung injury developing within hours after administration of mefloquine for a low-level Plasmodium falciparum malaria, which was persistent despite halofantrine therapy. Extensive microbiological investigation remained negative and video-assisted thoracoscopic lung biopsy demonstrated diffuse alveolar damage. The evolution was favourable without treatment. This is the second report of acute lung injury and diffuse alveolar damage caused by mefloquine. Glucose-;6-;phosphate dehydrogenase deficiency was present in the former case and was thought to contribute to the lung injury. However, glucose-phosphate dehydrogenase was normal in the present case, suggesting that it is not a predisposing condition to the lung injury.
Epidermal growth factor in the lungs of infants developing chronic lung disease
Authors: A.E. Currie, J.R. Vyas, J. MacDonald, D. Field, S. Kotecha
Journal: European Respiratory Journal (2001)

Growth factors important to lung growth and fibrosis have been poorly studied in chronic lung disease (CLD) of prematurity. Epidermal growth factor (EGF) promotes epithelial cell maturation, and vascular endothelial growth factor (VEGF) is important in angiogenesis. The concentration of these growth factors was determined in 111 bronchoalveolar lavage fluid (BALF) samples from 35 ventilated infants: 13 developed CLD (median gestation 27 weeks, birthweight 820 g), 16 developed and recovered from respiratory distress syndrome (RDS) (31 weeks, 1,415 g) and six control infants (33 weeks, 2,075 g) were ventilated for nonpulmonary reasons. At birth, EGF in BALF from the CLD and RDS infants was lower than in the control infants (control versus CLD, 7.3 versus 0.0 pg·mL −1 , p&lt;0.01; control versus RDS, 7.3 versus 5.0, p=0.08). EGF increased in all groups with a more rapid increase in control infants. A close relationship was noted between BALF EGF and gestational age (R=0.73). VEGF was undetectable at birth but increased at a similar rate in all three groups and did not correlate with gestation. In conclusion, these data suggest that epidermal growth factor is closely correlated to gestation and that it may predispose preterm infants to develop chronic lung disease.
Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis
Authors: T. Ishii, N. Keicho, S. Teramoto, A. Azuma, S. Kudoh, Y. Fukuchi, Y. Ouchi, T. Matsuse
Journal: European Respiratory Journal (2001)

Chronic obstructive pulmonary disease (COPD) and diffuse panbronchiolitis (DPB) are both characterized by chronic airflow limitation. Although the aetiology of these diseases is under investigation, it is commonly hypothesized that neutrophils have a major role in the disease pathogenesis. The variation of the genes related to chemotaxis of neutrophils may confer a risk for the development of both COPD and DPB. In the present report, the authors investigated the association between genetic variation that codes for the 416th and 420th amino acid of Gc-globulin, reported to be associated with chemotaxis of neutrophils, and susceptibility to COPD and DPB. Blood samples obtained from patients with COPD (n=63), DPB (n=82), and control subjects (n=82) were used for the genotyping assay. The proportion of GC*1F homozygotes was significantly higher in the COPD patients than the control subjects (COPD 36.5% versus control 20.7%), and the odds ratio for GC*1F homozygotes was 2.2 (95% confidence interval 1.1–4.6) for the COPD group. There was no difference on the distribution of the other genotypes (GC*1F-1S heterozygotes, GC*1S homozygotes, GC*2-1F heterozygotes, GC*2-1S heterozygotes and GC*2 homozygotes) or the allele frequencies among these groups. These findings suggest that the GC*1F gene polymorphism of Gc-globulin may be one of the risk factors for chronic obstructive pulmonary disease. However, no association between this polymorphism of Gc-globulin and susceptibility to diffuse panbronchiolitis was found.
The impact of meconium ileus on the clinical course of children with cystic fibrosis
Authors: A.K.C. Evans, D.A. Fitzgerald, K.O. McKay
Journal: European Respiratory Journal (2001)

The present study was designed to compare the clinical course of children diagnosed with cystic fibrosis (CF) in infancy due to the presence of meconium ileus (MI) with children diagnosed by way of a newborn screening programme (non-MI). A matched case-control study design was used. Matching was performed on the basis of sex and date of birth. All children born in New South Wales, Australia after 1980 and who had attended the CF clinic at The Children's Hospital at Westmead since diagnosis were included as possible cases or controls. Parameters pertaining to the clinical course were compared in 39 matched pairs. MI children had a significantly worse pulmonary status. The forced expiratory volume in one second was 16.3±5.2% higher (p&lt;0.001, n=21 pairs) and the forced vital capacity value 10.5±4.7% higher (p&lt;0.05, n=21 pairs) in non-MI children. The difference between the pairs (18.6±4.4 MI and 20.5±3.4 non-MI) in the Shwachman chest radiograph score was statistically significant (p&lt;0.05, n=39 pairs). There were no significant differences in any other assessed parameters, such as height, weight, the presence of liver function abnormalities, the frequency of hospitalization or airway microbial colonization. Meconium ileus may be an early indication of a more severe phenotype of cystic fibrosis. This was suggested by the significantly lower pulmonary function found in children with a history of meconium ileus compared to age- and sex-matched children who did not have meconium ileus.
Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension
Authors: E. Frisdal, V. Gest, A. Vieillard-Baron, M. Levame, H. Lepetit, S. Eddahibi, C. Lafuma, A. Harf, S. Adnot, M-;P. d'Ortho
Journal: European Respiratory Journal (2001)

Structural remodelling of pulmonary vessels is an important feature of pulmonary hypertension (PH), which reflects distal artery muscularization and matrix remodelling. The matrix metalloproteinases (MMPs) are involved in extracellular matrix turnover and hence, in smooth muscle cell migration and endothelial cell migration and proliferation. Among the MMPs, gelatinases (MMP-;2 and MMP-;9) can degrade basement membrane components and promote cell proliferation and migration. This study evaluated gelatinases in pulmonary vessels during progressive PH in two rat models: exposure to hypoxia or monocrotaline. Zymography of tissue homogenates revealed an association of progression of hypoxic PH with a time-dependent increase in gelatinase MMP-;2 activity, specific to pulmonary vessels. Increased MMP-;2 activity was also found 30 days postmonocrotaline. Reverse transcription polymerase chain reaction demonstrated upregulation of MMP-;2 messenger ribonucleic acid. Immunolocalization showed MMP-;2 throughout the pulmonary vasculature, from the trunk to the distal vessels, with strong staining of the intima, media and adventitia. MMP-;2 was found in its active form and gelatinolytic activity was correlated to PH severity. Activity localization by in situ zymography corroborated with the immunolocalization findings. In conclusion, the authors demonstrated that matrix metalloproteinase-;2 activity is increased in pulmonary vessels during progression of pulmonary hypertension, probably as a result of involvement in the matrix turnover associated with vascular remodelling during pulmonary hypertension.
Effect of luminal osmolarity on ion content of connective tissue in rat trachea after epithelial damage
Authors: A.J. Relova, G.M. Roomans
Journal: European Respiratory Journal (2001)

The authors investigated the physical role of the airway epithelium in response to changes in the airway surface fluid's composition by superperfusing the lumen with nonisotonic solutions. Morphological studies and measurements of changes in ion content in the underlying connective tissue (CT) were carried out. The study used an experimental model of isolated rat trachea. The trachea was mounted in an extraluminal organ bath with Ringer's solution, whereas the lumen was perfused with a fluid in which the NaCl concentration was varied. The tissue was fixed for electron microscopy or frozen for X-ray microanalysis. X-ray microanalysis showed that the Na and Cl content of the CT increased with increasing luminal NaCl concentrations. This increase was significantly larger when the tight junctions had been damaged by exposure to ethylene glycol tetra-acetic acid. At high luminal NaCl concentrations, electron microscopy showed that a significant influx of fluid into the CT had occurred in tracheae with damaged epithelia. Damage to the epithelium also resulted in ultrastructural changes in myofibroblasts, increased diameter of capillaries, and thickening of the basement membrane. The epithelium evidently plays a crucial role in the regulation of the ion content of the connective tissue in the airway wall, and epithelial damage may explain the greater sensitivity to provocation with hypersomolar sodium chloride solutions or airway dehydration observed in patients with asthma or cystic fibrosis.
Role of T- and B-;lymphocytes in pulmonary host defences
Authors: B.B. Moore, T.A. Moore, G.B. Toews
Journal: European Respiratory Journal (2001)

Pulmonary infectious diseases cause significant morbidity and mortality in both industrialized and developing countries. Adaptive immune responses are required to defend the lung against pathogens that survive in normal macrophages and extracellular organisms that evade phagocytosis. Microbes initiate both innate immune responses and specific adaptive immune responses. Innate immune response molecules regulate T-;lymphocyte differentiation. Activated T-;lymphocytes provide cytokines, which activate macrophages and lytic signals that lyse infected antigen-presenting cells. Antibodies produced by plasma cells facilitate microbial clearance through diverse effector mechanisms including opsonization, complement fixation and antibody-dependent cytotoxicity. Lymphocytes determine the specificity of the immune response and orchestrate effector limbs of the immune response.
Reference values for alveolar membrane diffusion capacity and pulmonary capillary blood volume
Authors: P. Zanen, I. van der Lee, T. van der Mark, J.M.M. van den Bosch
Journal: European Respiratory Journal (2001)

The reference values for diffusion capacity of the alveolar capillary membrane ( T m,CO ) and pulmonary capillary volume ( Q c ) are scarce, while the standard deviations of the equations are large. New equations and residual standard deviations (RSDs) were determined in a sample of healthy subjects. T m,CO and Q c values were measured in 117 (72 females, 45 males) nonsmoking healthy subjects. The carbon monoxide transfer factor ( T L,CO ) was determined when the volunteer was breathing room air and subsequently, when the volunteer was breathing 100% oxygen. From these data, T m,CO and Q c values were calculated. The females' T L,CO was 3.15 mmol·min −1 ·kPa −1 lower than the males', apparently caused by lower female lung volume. T m,CO and Q c were lower in females, but correction for lung volume eliminated this difference. Q c −1 reference equations for females and males, respectively, are 4.375×10 −2 −1.085×10 −2 ×height and 4.455×10 −2 −1.085×10 −2 ×height (RSD for both sexes: 2.544×10 −3 ). T m,Co −l reference equations for females and males, respectively, are 0.111+3.304×10 −4 ×age−4.753×10 −2 ×height and 0.127+3.304×10 −4 ×age−4.753×10 −2 ×height (RSD for both sexes: 1.085×10 −2 ). The general character of these equations complies with earlier publications, the only difference being that the RSDs are 1.18–2.76 times lower. New reference equations for diffusion capacity of the alveolar capillary membrane and pulmonary capillary volume are available with considerably smaller residual standard deviations.
Peak inspiratory flow rate and slope of the inhalation profiles in dry powder inhalers
Authors: M.E.A.C. Broeders, J. Molema, N.A. Vermue, H.Th.M. Folgering
Journal: European Respiratory Journal (2001)

Aerosol delivery depends on device design and inhalation technique. In vitro device evaluations have shown that the emitted dose and fine particle mass of dry powder inhalers (DPIs) increase at high peak inspiratory flow rates (PIFR). Since the PIFR is mostly achieved after the release of the powder, slope of the pressure profile is also described as an important determinant. The aim of the present study was to assess whether the PIFR while using Diskus® and Turbuhaler® inhalers could be used to predict the slope of the inhalation pressure profile. In a group of 10 stable asthma patients and three groups (mild, moderate and severe) of 16 chronic obstructive pulmonary disease (COPD) patients, lung function was measured, and for each device, 18 inhalation profiles were recorded with the inhalation profile recorder during six sessions over 10 weeks. The values for the pressure slope and PIFR of both Diskus® and Turbuhaler® were significantly correlated. The r-;values were 0.865 and 0.882, respectively (p&lt;0.01). Percentage explained variance was 74.8% for Diskus® and 77.8% for Turbuhaler®. Significant correlations were found between peak inspiratory flow rates and slopes. It has been shown for two different dry powder inhalers that peak inspiratory flow rate and slope correlate well in a wide range of patient groups.
Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence
Authors: E. von Mutius
Journal: European Respiratory Journal (2001)

There is increasing evidence from epidemiological studies to support the “hygiene hypothesis” with regard to the development of allergic diseases. This review will discuss the epidemiological findings relating to atopy and asthma, separately. The strongest arguments in favour of the “hygiene hypothesis” are the findings relating early life day care attendance to a significantly reduced risk of atopy and asthma, and the strong link between sibship size and the occurrence of atopy as confirmed by numerous studies. Furthermore, data relating serological immune responses to certain infections such as hepatitis A and Toxoplasma gondii suggest a role for such infections, or alternatively the lack of hygiene, to be operative in the inhibition of the development of allergic immune responses. The effects described seem to be stronger for atopy than for asthma. Furthermore, biological plausibility for such a hypothesis can be found from findings of recent in vitro studies and from animal experiments. Epidemiological studies attempting to identify single infections as being harmful or beneficial could fail, because it may be the total burden of microbial stimuli rather than a certain infection that directs the maturing immune system into a Th1-type T-;helper cell polarized response. The timing of the exposure seems to be essential for promoting beneficial or harmful effects, and may provide a “window of opportunity”.
A new method to perform quantitative measurement of bronchoscopic images
Authors: P.K. McFawn, L. Forkert, J.T. Fisher
Journal: European Respiratory Journal (2001)

Bronchoscopy is a commonly used clinical tool that provides a direct image of the bronchial lumen. However, bronchoscopy has seen little use as a quantitative measurement tool, mainly because of the wide-angle lens which distorts the image. The present authors have tested the ability of numerical algorithms and commercial software to correct for this distortion. Test objects of known size were imaged with four different bronchoscopes. Commercial image analysis software was used to measure the size of features in the images before and after applying distortion correction algorithms. The technique was then applied by measuring airway narrowing in anaesthetized pigs during vagal stimulation. Without correction, object size near the edge of the field of view is underestimated by ∼40%. The error in measured diameter of concentric circles was dependent on the radius of the circle, increasing to 25% for circles occupying 90% of the field. Third order polynomial functions were required to correct these errors. After correction, errors were independent of object size or location in the image. Correction for lens distortion was independent of the distance between bronchoscope and object. The authors conclude that modern image processing software can correct for the distortion produced by wide-angle bronchoscope lenses.
Lipid-laden macrophage index and inflammation in bronchoalveolar lavage fluids in children
Authors: M.Y. Kazachkov, M.S. Muhlebach, C.A. Livasy, T.L. Noah
Journal: European Respiratory Journal (2001)

The presence of lipids in alveolar macrophages has been used clinically as an indicator of aspiration, a process associated with increased lung inflammation in animal models. The hypothesis is that the quantity of lipids in alveolar macrophages, measured as lipid-laden index (LLI), would correlate with lung inflammation in paediatric patients. Children with chronic respiratory symptoms (21 cystic fibrosis (CF), 24 non-CF) underwent flexible bronchoscopy with bronchoalveolar lavage (BAL) and 24-;h intra-oesophageal pH monitoring for clinical indications. Total cell counts, number and per cent of neutrophils and macrophages, and LLI were determined in the bronchoalveolar lavage fluids (BALF) from all children. BALF were also obtained from eight healthy, young nonsmoking adults for comparison. LLI in non-CF children were 6.9±3.5 (mean±sem) which were higher than LLI in healthy adults (1.0±0.4), (p=0.045). Children with CF had very high LLIs (19.2±4.5) compared with both healthy adults (p=0.014) and children without CF (p=0.045). LLI did not correlate with airway inflammation in any group. LLI in children with abnormal pH probes had a tendency to be higher than in children with normal pH probes, but the difference was not significant (p=0.098). It is concluded that the lipid-laden index was significantly elevated in children with chronic respiratory symptoms compared with healthy adults, and in children with cystic fibrosis compared with those who have other chronic respiratory conditions. However, the lipid-laden index did not correlate with the quantity of bronchoalveolar lavage fluid inflammation. The lipid-laden index in children may, in part, reflect processes other than aspiration, such as airways obstruction.
Skeletal Muscle Tissue Engineering: from Tissue Regeneration to Biorobotics.
Authors: Maira Zoe Cordelle, Sarah JB. Snelling, Pierre-Alexis Mouthuy
Journal: Cyborg and Bionic Systems (2025)

With its remarkable adaptability, energy efficiency, and mechanical compliance, skeletal muscle is a powerful source of inspiration for innovations in engineering and robotics. Originally driven by the clinical need to address large irreparable muscle defects, skeletal muscle tissue engineering (SMTE) has evolved into a versatile strategy reaching beyond medical applications into the field of biorobotics. This review highlights recent advancements in SMTE, including innovations in scaffold design, cell sourcing, usage of external physicochemical cues, and bioreactor technologies. Furthermore, this article explores the emerging synergies between SMTE and robotics, focusing on the use of robotic systems to enhance bioreactor performance and the development of biohybrid devices integrating engineered muscle tissue. These interdisciplinary approaches aim to improve functional recovery outcomes while inspiring novel biohybrid technologies at the intersection of engineering and regenerative medicine.
Future risk projection to engage ‘near-miss’ individuals in lung cancer screening eligibility: an analysis of ILST data
Authors: Chellan Kumarasamy, Kim Betts, Richard Norman, Annette McWilliams, Emily Stone, David C L Lam, Renee Manser, Paul Fogarty, Henry M Marshall, Stephen Lam, Martin Tammemagi, Kwun M Fong, Sukhinder Atkar-Khattra, Fraser Brims
Journal: Thorax (2025)

Introduction Lung cancer risk increases with time, and participants who are initially ineligible for lung cancer screening (LCS) could become eligible later. The aim of this study was to determine the proportion of people (initially ineligible) who may become eligible in a risk model-based LCS programme and the impact smoking cessation could have on this cohort. Methods All potential participants for the International Lung Screening Trial aged 55–80 years, ineligible for Low-dose CT screening at baseline (PLCO m2012 &lt;1.5% 6-year risk), were included. Assuming annual increments of change in age, smoking duration and quit time, and under the assumption of other risk variables being constant, projections of risk were made using the PLCO m2012 model from evaluation to the upper age limit of 80 years. Results 4451 subjects with a median age of 61 (IQR: 57–66) years were included. Assuming no change in smoking status post evaluation, 2239 participants (50.3%) became eligible (PLCO m2012 ≥1.51%) by age 80, with 26.9% and 38.7% of the cohort reaching eligibility by age 70 and 75 years, respectively. Among participants with a baseline risk≥0.6%, 1518 (34.1%) reached eligibility within 10 years of initial evaluation. Smoking cessation after first evaluation can reduce the proportion of individuals who may become eligible for LCS by age 70 from 68.7% to 24.9%. Conclusions Future risk projection of eligibility could provide a time window for reassessment of risk on an individual level. It is important to provide smoking cessation services to individuals who are ineligible for LCS at the initial programme contact.