bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphocyte activation after exposure to swine dust: a role of humoral mediators and phagocytic cells
Authors: Müller-Suur C. , Larsson P.H. , Larsson K. , Grunewald J.
Published: October 2002

Exposure to swine dust causes intense airway inflammation with multifold increase in inflammatory cells and secretion of pro-inflammatory cytokines. Thisin vitrostudy focuses on the swine-dust activation of lymphocytes in whole blood, in phagocyte-depleted whole blood and in peripheral blood mononuclear cells (PBMC), in order to investigate whether phagocytic cells and/or soluble mediators are involved in the activation of T-cells following exposure to organic dust from a swine confinement house.

T-cell activation was analysed by flow cytometry with double staining for CD3 and the activation marker CD69.

Swine dust (50 µg) incubated (24 h) with heparinized whole blood was shown to activate 27.6% of the T-cells, while swine dust incubated with whole blood depleted from phagocytic cells or PBMC only activated 4.5% and 4.8% of the T-cells, respectively. Plasma separated from whole blood preincubated with swine dust for 24 h stimulated as much as 32.4% of PBMC T-cells and contained high levels of interleukin (IL)-12 (14 pg·mL) and interferon (IFN)-γ (2284 pg·mL−1), while plasma from PBMC incubated with swine dust contained low levels of IL-12 (2 pg·mL−1) and IFN-γ (196 pg·mL−1).

This study demonstrates that activation of T-cells by organic dust from a swine confinement building seems to require phagocytic cells, most likely acting through the release of soluble mediators. Also, conditioned plasma from swine-dust exposed whole blood, which was capable of activating T-cells, contained high concentrations of interleukin-12 and interferon-γ.
Correlation of inhaled nitric-oxide induced reduction of pulmonary artery pressure and vascular changes
Authors: Jiang B.H. , Maruyama J. , Yokochi A. , Amano H. , Mitani Y. , Maruyama K.
Published: October 2002

The purpose of the present study was to determine the relationship between hypertensive pulmonary vascular remodelling and the changes in mean pulmonary artery pressure (mPAP) during low-dose nitric oxide (NO) inhalation.

Rats were exposed to chronic hypobaric hypoxia (air at 50.5 kPa (380 mmHg), 10% oxygen, for 5–29 days) to induce chronic pulmonary hypertension (PH) with pulmonary vascular structural changes. After the chronic hypoxic exposure, the rats had an indwelling pulmonary artery catheter inserted and changes in mPAP with NO were correlated to morphometrical analysis of pulmonary vascular changes.

All concentrations of inhaled NO (0.1–2.0 parts per million) reduced mPAP with a similar per cent reduction from baseline mPAP in PH rats, while no changes were observed in control rats. During NO inhalation in PH rats, the absolute value of the decrease in mPAP, but not per cent reduction in mPAP, significantly correlated with baseline mPAP, the percentage of muscularised arteries at the alveolar wall level and at the alveolar duct level, and the per cent medial wall thickness of muscularised arteries.

In the chronic hypoxic pulmonary hypertension model, the severity of pulmonary vascular remodelling did not alter the reactivity of the pulmonary arteries to nitric oxide and might, in part, determine the magnitude of nitric-oxide induced absolute reduction in mean pulmonary artery pressure.
Activation of second messenger pathways in alveolar macrophages by endotoxin
Authors: Monick M.M. , Hunninghake G.W.
Published: October 2002

The alveolar macrophage plays an important role in immune surveillance of the lung. Early responses to infectious agents by macrophages can decrease tissue injury and promote recovery of the host. Macrophage responses to pathogens are the cornerstone of the innate or nonspecific immune system. In particular, the response of macrophages to endotoxin from Gram negative bacteria has been the focus of many recent studies. The recent discovery of the endotoxin receptor has accelerated the study of signalling in macrophages. This review focuses on the downstream events that occur following exposure of the alveolar macrophage to endotoxin.
Repeated allergen exposure changes collagen composition in airways of sensitised Brown Norway rats
Authors: Palmans E. , Pauwels R.A. , Kips J.C.
Published: October 2002

Increased or altered collagen deposition in the airway wall is one of the characteristics of airway remodelling in asthma. The mechanisms underlying this increase, and its functional consequences remain to be established further. Representativein vivoanimal models might be useful in this respect.

In the present study, collagen deposition after prolonged allergen exposure was characterised in the airway wall of Brown Norway rats. Sensitised rats were repeatedly exposed to ovalbumin (OA) or phosphate-buffered saline during 2 and 12 weeks.

The deposition of collagen type I, III, IV, V and VI was not altered in animals exposed to OA for 2 weeks. After 12 weeks of OA exposure, more collagen type I was deposited in the inner and outer airway wall and more type V and VI collagen was observed in the outer airway wall. At 12 weeks the number of vessels, identifiedviatype IV collagen staining was not increased, but the total vessel area was.

In conclusion, prolonged allergen exposure in sensitised rats is associated with enhanced deposition of type I, V and VI collagens and increased vascularity. This suggests that some aspects of airway remodelling in asthma could be driven by long-term allergen exposure.
Pulmonary arterial hypertension and type-I glycogen-storage disease: the serotonin hypothesis
Authors: Humbert M. , Labrune P. , Sitbon O. , Le Gall C. , Callebert J. , Hervé P. , Samuel D. , Machado R. , Trembath R. , Drouet L. , Launay J-M. , Simonneau G.
Published: October 2002

A case of pulmonary arterial hypertension in a patient with type-Ia glycogen-storage disease, a rare autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase is reported in this study. It has been suggested that the occurrence of pulmonary arterial hypertension in type-Ia glycogen-storage disease could be due to an abnormal production of vasoconstrictive amines such as serotonin.

To test this hypothesis, plasma serotonin concentrations were prospectively measured in 13 patients with type-Ia glycogen-storage disease, one patient with severe pulmonary hypertension and type-Ia glycogen-storage disease, 16 patients displaying severe pulmonary arterial hypertension, and 26 normal healthy controls.

Elevated plasma serotonin concentrations were found in patients with either severe pulmonary arterial hypertension (38.8±7.3 nmol·L−1) or type-Ia glycogen-storage disease (36.8±11.5 nmol·L−1), as compared with controls (8.8±0.6 nmol·L−1, p<0.001). Plasma serotonin was dramatically elevated in the patient with type-Ia glycogen-storage disease and pulmonary arterial hypertension (113.4 nmol·L−1).

It is concluded that type-Ia glycogen-storage disease may be another condition in which abnormal handling of serotonin is one event in a multistep process leading to severe pulmonary arterial hypertension.
Transbronchial biopsy as a tool to evaluate small airways in asthma
Authors: Balzar S. , Wenzel S.E. , Chu H.W.
Published: October 2002

Small airway (SA) inflammation in asthmatics is poorly understood. Surgical biopsies to obtain peripheral lung tissue are seldom justified in asthmatics. Therefore, the authors hypothesised that transbronchial biopsy could be an alternative approach to evaluate SA in asthma.

Transbronchial and endobronchial biopsy tissue samples (TBBX and EBBX) from 12 severe asthmatics were evaluated for airway and parenchymal total inflammatory cell count expressed as the sum of immunostained T‐cells (CD3), macrophages (CD68), mast cells (tryptase AA1), neutrophils (neutrophil elastase) and eosinophils (EG2) per mm2. The large airways (LA) were evaluated in EBBXs, while SA, medium airways (MA) and alveolar tissue (AT) were evaluated in TBBXs.

When cell counts from SA, MA, LA and AT were compared, SA had a significantly higher cell count than MA or LA (SA 1011·mm−2(539–1,290), MA 346·mm−2(223–415), LA 332·mm−2(189–416), AT 464·mm−2(298–834)). The cell density and pattern of the inflammatory cell distribution in subjects with TBBXs appeared similar to those in three severe asthmatics whose inflammatory cells were analysed in surgical tissue samples.

This study suggests that small airway may be identified and analysed in transbronchial biopsy tissue samples and therefore transbronchial biopsy tissue samples could expand the analysis of inflammation and tissue remodelling in asthma.
NOS and COX isoforms and abnormal microvessel responses to CO2and H+in hyperoxia-injured lungs
Authors: Naoki K. , Kudo H. , Suzuki K. , Takeshita K. , Miyao N. , Ishii M. , Sato N. , Suzuki Y. , Tsumura H. , Yamaguchi K.
Published: October 2002

The aim of the present study was to compare microvessel responses to hypercapnic and isocapnic acidosis in hyperoxia-injured lungs and to assess the role of constitutive and inducible forms of nitric oxide synthase (NOS) and cyclo-oxygenase (COX).

Real-time confocal luminescence microscopy was used to measure changes in the diameter of acinar arterioles, venules and capillaries in response to stimulation with hypercapnic and isocapnic acidosis in isolated rat lungs injured by 90% oxygen exposure for 48 h. Observations were made with and without inhibition of constitutive (endothelial constitutive NOS (ecNOS) and COX‐1) and inducible isoforms (iNOS and COX‐2) of NOS and COX. Upregulation of NOS was assessed by measuring enzyme levels in lung homogenates by Western blot analysis and enhancement of the COX-related pathway was judged from perfusate concentrations of 6‐ketoprostaglandin F1α.

ecNOS and COX‐1, but not iNOS and COX‐2, were upregulated in hyperoxia-injured lungs. The nitric oxide produced by ecNOS attenuated COX‐1 activity in injured arterioles and venules, but carbon dioxide enhanced it, leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition. Although a high hydrogen ion concentration was unnecessary for excitation of COX‐1, venule constriction in response to H+was enhanced by COX‐1 inhibition.

Constitutive, but not inducible, isoforms of cyclo-oxygenase and nitric oxide synthase play an important role in abnormal microvessel responses to carbon dioxide and hydrogen ions in hyperoxia-injured lungs.
Efficiency of cold passover and heated humidification under continuous positive airway pressure
Authors: Randerath W.J. , Meier J. , Genger H. , Domanski U. , Rühle K‐H.
Published: October 2002

Cold passover and heated humidifiers are employed for the prevention of side-effects associated with continuous positive airway pressure (CPAP) treatment. However, to date, it has not been possible to separately measure the humidity of inspired and expired air. The aim of this study was to compare the relative humidity of the inspired air and the water loss during respiration between cold passover and heated humidifiers under CPAP.

Humidity and temperature were determined separately for the respiratory phases, without humidification, with cold passover and heated humidifiers in 10 healthy subjects. Humidity was measured with a capacitive hygrometer, temperature with a “Type K” thermosensor, and impedance of the total respiratory system with impulse oscillometry.

The relative humidity (rH) of the inspired air (mean±sd) increased significantly from 24.0±9.1% rH (34.8±1.0°C, no humidifier) to 34.5±10.1% rH (34.6±1.0°C) under cold humidification, and to 53.9±13.2% rH (35.0±1.1°C) under heated humidification. With heated humidification, water loss was reduced by 38% compared to cold humidification. The impedance increased from 5.7±1.8 cmH2O·L·s−1(no humidifier) to 6.7±1.8 cmH2O·L·s−1(heated humidifier).

The authors conclude that the use of a heated humidifier during continuous positive airway pressure appreciably increases the relative humidity of the inspired air and reduces the water loss during respiration.
Bronchial epithelial cell B7-1 and B7-2 mRNA expression after lung transplantation: a role in allograft rejection?
Authors: Elssner A. , Jaumann F. , Wolf W-P. , Schwaiblmair M. , Behr J. , Fürst H. , Reichenspurner H. , Briegel J. , Niedermeyer J. , Vogelmeier C.
Published: October 2002

Obliterative bronchiolitis is commonly interpreted as chronic rejection and involves the bronchial and bronchiolar epithelium. Upregulation of major histocompatibility complex (MHC) II on bronchial epithelial cells (BEC) had been hypothesised to be an important trigger of a bronchus directed rejection response. More recently, the additional expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells were found to play an important role in the activation of T-lymphocytes in transplant rejection. The role of the expression of these molecules by BEC is unclear.

BEC obtained by bronchial brushing and bronchoalveolar lavage fluid (BALF) cells from lung transplant recipients were studied and evaluated for messenger ribonucleic acid (mRNA) expression of B7-1 and B7-2 by semi-quantitative reverse transcriptase-polymerase chain reaction. Significantly elevated B7-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios were found in BEC from patients examined during the first 3 months after lung transplantation. Interestingly, in a small group of patients with bronchiolitis obliterans syndrome the B7-1/GAPDH and B7-2/GAPDH ratios were significantly elevated for BEC, whereas no differences were found for the BALF cells.

In summary, B7 messenger ribonucleic acid expression by bronchial epithelial cells may play a role in (chronic) lung allograft rejection.
MRI of the pharynx and treatment efficacy of a mandibular advancement device in obstructive sleep apnoea syndrome
Authors: Sanner B.M. , Heise M. , Knoben B. , Machnick M. , Laufer U. , Kikuth R. , Zidek W. , Hellmich B.
Published: October 2002

In obstructive sleep apnoea syndrome (OSAS), prosthetic mandibular advancement devices (MAD) seem to be a promising treatment alternative to conventional continuous positive airway pressure therapy. Unfortunately, while they are effective in some patients, they are ineffective in others or may even worsen OSAS. At present, it is not known whether predictors can be defined which allow for estimation of the potential effect of oral appliances on the severity of OSAS.

Clinical and polysomnographical efficacy of a MAD was evaluated in 15 patients with OSAS. In addition, ultrafast magnetic resonance imaging (MRI) of the pharynx was performed in 13 of these patients at rest during transnasal shallow respiration and during performance of the Muller manoeuvre, both with and without the MAD, and the site of closure was determined.

The MAD reduced the mean apnoea/hypopnoea index (AHI) from 19.8±14.5 to 7.2±7.4·h−1. Seven subjects (53.8%) had at least a 50% reduction in AHI to a value <10·h−1with the MAD, whereas the MAD was ineffective in six patients. Five of the seven treatment responders had no significant pharyngeal obstruction during the manoeuvre with the device, while all of them had pharyngeal obstruction when not equipped with the device. Four of the six patients with treatment failure had a single velopharyngeal obstruction and two a combined obstruction of the velo‐ and glossopharynx during the Muller manoeuvre while wearing the device.

The results of this study suggest that airway patency during the Muller manoeuvre while wearing a mandibular advancement device may be predictive of the success of obstructive sleep apnoea syndrome treatment with a mandibular advancement device.
Environmental tobacco smoke and health in the elderly
Authors: Jaakkola M.S.
Published: October 2002

The aims of this article are to synthesize the evidence on health effects of environmental tobacco smoke (ETS) in the elderly and to discuss questions for future research. Health effects are divided into aetiological and prognostic studies.

There is convincing evidence that ETS causes lung cancer and coronary heart disease, both of which are diseases of the elderly. Several cross-sectional studies show increased occurrence of chronic respiratory symptoms and deficits in ventilatory lung function in relation to ETS exposure at home and/or at work.

A limited number of studies have found significant relations between ETS exposure and asthma, chronic obstructive pulmonary disease (COPD), pneumococcal infections and stroke in the elderly. Longitudinal studies are needed before any definite conclusions can be made concerning ETS and noncarcinogenic respiratory diseases in the elderly.

The potential role of environmental tobacco smoke exposure as a prognostic factor determining development of a pre-existing respiratory or heart disease is an important new area for research.
Fever episodes in early life and the development of atopy in children with asthma
Authors: Calvani M. , Alessandri C. , Bonci E.
Published: October 2002

The hygiene hypothesis proposes that declining exposure to infections may contribute to the allergy and asthma “epidemic”, but studies to identify the infections involved have so far provided conflicting data. An alternative approach could be based on an attempt to identify the mechanisms common to several different infections, which may exert an atopy “protective” effect. One of these mechanisms may be fever, which is frequently associated with infections and may stimulate the synthesis of interferon‐γ. The aim of this study was to test whether the frequency of fever episodes in the first years of life are related to the development of atopy.

Asthmatic (cases, n=317) and nonasthmatic children (controls, n=304) attending the outpatients' allergy clinic were enrolled. The number of fever episodes in the first 2 yrs of life was retrospectively assessed by parental reportviaa questionnaire completed by interview. Atopy was determined by skin-prick tests to 10 prevalent inhalant allergens at the time of examination.

Fever episodes in the first or in the second year of life were significantly more frequent among children with asthma. However, this difference was totally accounted for by a subgroup of children who started wheezing in the first 12 months of life. A significant inverse association between fever episodes in the first 12 months of life and atopy was found among cases, but not in controls. The association persisted after adjusting for age, sex, daycare attendance and family history of atopic disease and this was totally accounted for by asthmatic children who started wheezing after the first 12 months of life. No significant association was found between fever episodes in the second year of life and atopy for cases and controls.

The data presented here suggests that fever episodes early in life may affect the natural history of asthma by preventing the development of atopy and highlights the need to monitor fever episodes of any kind in longitudinal studies aimed at investigating the hygiene hypothesis prospectively.
Overexpression of matrix metalloproteinase‐8 and ‐9 in bronchiectatic airwaysin vivo
Authors: Zheng L. , Lam W.K. , Tipoe G.L. , Shum I.H. , Yan C. , Leung R. , Sun J. , Ooi G.C. , Tsang K.W.
Published: October 2002

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process.

Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP‐8 and MMP‐9 in bronchiectatic airwaysin vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP‐8, MMP‐9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell·mm−2of the lamina propria by using an image analysis system.

There were significantly higher densities of MMP‐8 and MMP‐9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP‐8 and MMP‐9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP‐8 with neutrophil and MMP‐9 with macrophage densities.

An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.
Nitric oxide but not carbon monoxide is continuously released in the human nasal airways
Authors: Lundberg J.O.N. , Palm J. , Alving K.
Published: October 2002

Results from different laboratories indicate that nitric oxide (NO) and carbon monoxide (CO) coexist in the human airways both in health and disease. These gases are present in exhaled human breath and high concentrations of NO as well as CO have been reported in the nasal airways. In addition, exhaled CO and NO are increased in patients with airways inflammation. NO and CO were measured simultaneously in orally exhaled air and in air sampled from the nose in 18 healthy subjects using chemiluminescence (for NO) and infrared (for CO) techniques at different fixed flow rates. The acute effects of smoking on airway release of NO and CO were also studied.

Nasal NO was detected in all subjects and the concentrations were highly flow-dependent (mean±sem: 236±23 and 527±49 parts per billion (ppb), at 2 and 0.5 L·min−1, respectively). In contrast, no evidence of CO release in the nasal airways regardless of sample flow rate was found. In fact, additional experiments indicated a net absorption of CO when low levels of this gas were flushed through the nasal cavity. Nasal CO also remained undetectable after smoking. Both NO (22±2 ppb) and CO (1.1±0.1 parts per million) were consistently found in orally exhaled air. CO, but not NO, levels increased acutely after smoking a cigarette.

The authors conclude that the patterns of nitric oxide and carbon monoxide release in the airways seem to differ profoundly in healthy subjects. Orally exhaled air contains both nitric oxide and carbon dioxide whereas nasal air contains nitric oxide only.
Negative-pressure ventilation: is there still a role?
Authors: Corrado A. , Gorini M.
Published: October 2002

Negative-pressure ventilation (NPV) was the primary mode of assisted ventilation for patients with acute respiratory failure until the Copenhagen polio epidemic in the 1950s, when, because there was insufficient equipment, it was necessary to ventilate patients continually by handviaan endotracheal tube. Thereafter, positive-pressure ventilation was used routinely. Since it was also observed that patients with obstructive sleep apnoea could be treated noninvasively with positive pressureviaa nasal mask, noninvasive positive-pressure ventilation (NPPV) has become the most widely used noninvasive mode of ventilation.

However, NPV still has a role in the treatment of certain patients. In particular, it has been used to good effect in patients with severe respiratory acidosis or an impaired level of consciousness, patients that to date have been excluded from all prospective controlled trials of NPPV. NPV may be used in those who cannot tolerate a facial mask because of facial deformity, claustrophobia or excessive airway secretion.

NPV has also been used successfully in small children, and beneficial effects on the cardiopulmonary circulation maybe a particular advantage in children undergoing complex cardiac reconstructive surgery.

This review is divided into two parts: the first is concerned with the use of negative-pressure ventilation in the short term, and the second with its use in the long term.
Tumour necrosis factor‐α induced CD70 and interleukin‐7R mRNA expression in BEAS‐2B cells
Authors: Wolf K. , Schulz C. , Riegger G.A.J. , Pfeifer M.
Published: October 2002

Over the past few years, evidence has emerged for the potential role of the human bronchial epithelial cell in the initiation and progress of inflammation of the airway.

Thus, the aim of this study was to investigate the expression pattern of cytokines and immunomodulatory factors in the human bronchial epithelial cell. To elucidate this highly complex expression and regulation pattern, the simian virus‐40 transformed human bronchial-epithelial cell line BEAS‐2B was stimulated with human recombinant tumour necrosis factor (hrTNF)‐α (10 ng·mL−1(specific activity, 2.86×107 U·mg−1)) and messenger ribonucleic acid (mRNA) expression pattern was analysed by complementary deoxyribonucleic acid (cDNA) array analysis.

Among 375 arrayed cDNA clones, 173 (46%) were detected in BEAS‐2B cells. The levels of expression of 17 genes, including those of monocyte chemoattractant protein (MCP)‐1, intercellular adhesion molecule (ICAM)‐1, growth-related oncogene (GRO) α, β, γ, interleukin (IL)‐7 receptor, CD70, IL‐6, IL‐8, granulocyte-macrophage colony-stimulating factor (GM‐CSF) and regulated in activation, normal T‐cell expressed and secreted (RANTES) were elevated after TNF‐α stimulation. The differential character of 12 clones was further characterised and verified by real time polymerase chain reaction (PCR) analysis of total ribonucleic acid (RNA) isolated from BEAS‐2B cells after 4 or 16 h incubation with increasing TNF‐α concentrations (1 pg–10 ng·mL−1). The authors semiquantified concentration-dependent mRNA upregulation of cytokines and immunology factors identified in the array and could determine threshold values of mRNA increases at 10 pg·mL−1–1 ng·mL−1TNF‐α by real-time PCR.

For CD70 (CD27 ligand) and interleukin‐7 receptor, which to the best of the author's knowledge have not yet been described in the human bronchial epithelial cell, a rapid and continuous messenger ribonucleic acid increase induced by 100 pg·mL−1tumour necrosis factor‐α after only 60–90 min was shown. A potential role for these genes in the inflammatory process in the human bronchial epithelial cell is proposed.
β‐adrenergic receptor-mediated growth of human airway epithelial cell lines
Authors: Nishimura K. , Tamaoki J. , Isono K. , Aoshiba K. , Nagai A.
Published: October 2002

Abnormal growth of airway epithelium and the resultant thickening of airway walls may produce narrowing of airway calibre, thereby contributing to deterioration of bronchoconstriction in chronic obstructive pulmonary disease (COPD). β2‐adrenergic agonists have been widely used for the treatment of COPD, but their effects on the growth of airway epithelial cells is unknown.

Growth of three human airway epithelial cell lines was studiedin vitro. Exposure to salbutamol in serum-free medium increased 3‐(4,5-dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium-bromide reduction and intracellular deoxyribonucleic acid (DNA) contents in 16-human bronchial epithelium (16-HBE) cells and NCI-H292 cells, but not in A549 cells. The growth-promoting effect of salbutamol in 16-HBE cells was equipotent to 10% foetal bovine serum and was inhibited by propranolol and a cyclic adenosine monophosphate (cAMP) antagonist, Rp-adenosine 3′,5′-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS). Likewise, forskolin and 8‐bromoadenosine 3′,5′-cyclic monophosphate (8‐Br-cAMP) caused cell growth and DNA synthesis. Western blot analysis showed that salbutamol, forskolin, and 8‐Br-cAMP each induced expression of the phosphorylated form of mitogen-activated protein (MAP) kinase, and that the salbutamol-induced phosphorylation was inhibited by propranolol, Rp-cAMPS, and the MAP kinase-kinase inhibitor PD98059.

These results suggest that in certain airway epithelial cell lines stimulation of β2‐adrenergic receptors and the consequent production of cyclic adenosine monophosphate may upregulate cell growth, probably through activation of the mitogen-activated protein kinase cascade.
Endobronchial ultrasound in therapeutic bronchoscopy
Authors: Herth F. , Becker H.D. , LoCicero J. , Ernst A.
Published: October 2002

Endobronchial ultrasound (EBUS) has been introduced as an adjunct to diagnostic bronchoscopy as it allows evaluation of the submucosal and parabronchial structures. Its use in therapeutic bronchoscopy has not been assessed. A large observational study of the value of EBUS in therapeutic bronchoscopy is presented here.

From January 1998–January 2001 all patients undergoing therapeutic bronchoscopy and EBUS were evaluated prospectively. Patient demographics, indication for bronchoscopy, interventional treatments used and changes in therapy as influenced by the use of EBUS were documented. A total 2,446 therapeutic bronchoscopies were performed. In 1,174 cases EBUS was used (29% mechanical tumour debridement, 20% airway stenting, 13% Neodymium:yttrium aluminium garnet (Nd:YAG) laser use, 23% argon plasma coagulation, 11% brachytherapy, 2% foreign body removal and 2% endoscopic abscess drainage).

EBUS guided or changed therapy significantly in 43% of cases. Changes included adjustment of stent dimensions, termination of tumour debridement when nearing vessels, and referral for surgical interventions rather than endoscopic treatment. Complications associated with EBUS use were minimal. No patient undergoing EBUS guided tumour destruction experienced severe bleeding or fistula formation.

In summary, endobronchial ultrasound was easily performed and changed or guided therapeutic decisions during therapeutic bronchoscopic procedures in a substantial number of cases. As this may result in better outcomes, it has become a standard adjunct in the authors practice.
Weakness of respiratory and skeletal muscles after a short course of steroids in patients with acute lung rejection
Authors: Nava S. , Fracchia C. , Callegari G. , Ambrosino N. , Barbarito N. , Felicetti G.
Published: October 2002

There have been occasional reports of acute respiratory and skeletal muscle weakness in intensive care unit patients treated with massive doses of corticosteroids. However, in this setting the concomitant use of other drugs may have influenced the finding.

In this study the effects of 5 days of treatment with high doses of steroids in consecutive patients with acute lung rejection after transplantation were systematically evaluated. Maximal inspiratory pressure during phrenic nerve stimulation and peak torque of isokinetic contraction of the quadriceps and hamstring muscles were measured objectively.

Compared to the pretreatment condition, ∼45% of patients showed acute generalised muscle weakness that recovered after ∼2 months.

This demonstrates muscle weakness induced by steroids within patients.
Antioxidant intake and adult-onset wheeze: a case-control study. Aberdeen WHEASE Study Group
Authors: Bodner C , Godden D , Brown K , Little J , Ross S , Seaton A
Published: October 2002

An increase in prevalence of wheezing illness in the UK has coincided with a reduction in the consumption of natural antioxidants, which may modulate the lung's response to oxidant stress, limiting the expression of airway inflammation and respiratory symptoms. The hypothesis that intakes and plasma levels of natural antioxidants would be determinants of adult-onset wheezing illness was tested. A nested case-control study was conducted in 94 cases with adult-onset wheeze and 203 controls aged 39-45 yrs identified in a 30-yr follow-up survey. Antioxidant intake was measured by a food frequency questionnaire, and plasma and red cell measurements of antioxidant status were obtained. Outcome measures were onset of wheeze since age 15 yrs (ever wheeze) and wheeze occurring in the past 12 months (current wheeze). After adjusting for the effects of smoking, socioeconomic status, atopy, family history of atopic disease and total energy intake, intakes of vitamin E (odds ratio (OR) = 4.02 for low compared to high tertile of intake) and plasma levels of ascorbate (OR = 0.98 per unit) and alpha-tocopherol:triglyceride ratio (OR = 0.34 per log(e) unit) were inversely related to adult-onset wheeze. In analyses stratified by social class and smoking, intakes of vitamin C and E and plasma levels of ascorbate and alpha-tocopherol:triglyceride ratio were inversely related to current wheeze in the manual social class and among current smokers. No independent associations of vitamin A, beta-carotene or total plasma antioxidant capacity were found. The results support the hypothesis that deficiencies of vitamins C and E are associated with wheezing symptoms. Smokers in the manual social class are particularly susceptible to these effects.
Lung status in young Danish rurals: the effect of farming exposure on asthma-like symptoms and lung function
Authors: Omland O , Sigsgaard T , Hjort C , Pedersen OF , Miller MR
Published: October 2002

The aim of this study was to assess the prevalence of asthma (self-reported) and relate this to lung function and factors associated with asthma in young farmers. Two hundred and ten female and 1,691 male farming students together with 407 males controls were studied. Each subject underwent a medical interview; forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were recorded using a dry wedge spirometer. Histamine bronchial reactivity was measured using the Yan method. Skin prick testing was performed using inhalant allergens. Nonsmokers had lower prevalence of asthma (5.4-10.8%) than smokers (11.3-21.0%) (p<0.05). Females reported symptoms of asthma nearly twice as often as males. Sex, smoking and a family history of asthma/allergy were significantly associated with asthma. Controls had higher standardized FEV1 and FVC residuals than male students, both nonsmokers (0.21 and 0.24) versus (-0.06 and -0.05) and smokers (0.29 and 0.33) versus (-0.11 and 0.13) (p<0.032). Bronchial hyperresponsiveness, asthma, siblings with allergy and working with cattle (controls only) were significantly associated with reduced lung function. In conclusion, the prevalence of asthma was significantly related to smoking, female sex, family history of asthma and allergy. Whilst bronchial hyperresponsiveness was associated with reduced lung function and lung function was slightly reduced in the male farming students, there was no association found between occupational farming exposure and either lung symptoms or lung function.
Reduced intracellular magnesium concentrations in asthmatic patients
Authors: Emelyanov A , Fedoseev G , Barnes PJ
Published: October 2002

Magnesium is important in the regulation of bronchomotor tone, and low dietary intake of magnesium has been associated with airway hyperresponsiveness in epidemiological studies. The concentration of magnesium in serum, erythrocytes and urine in 49 patients with asthma (29 males, aged 15-65 yrs) and in 25 normal subjects (15 males, aged 17-36 yrs) was studied by atomic absorption. Magnesium concentrations were significantly lower in erythrocytes and urine in both atopic (n = 26) and nonatopic (n = 23) asthmatic patients as compared with the control group, whereas serum concentrations did not differ. The concentration of magnesium in erythrocytes was not related to the degree of airway obstruction as measured by forced expiratory volume in one second (FEV1) but was significantly correlated with airway hyperresponsiveness measured as the provocative concentration causing a 20% fall in FEV1 to inhaled acetylcholine (r = 0.64; p<0.05). In addition, a magnesium tolerance test showed increased retention of magnesium (58.9% of administered dose in asthmatic patients compared with 8.9% in normal subjects, p<0.05). In conclusion, the low cellular concentration of magnesium may be associated with airway hyperresponsiveness in asthmatic patients.
Theophylline induces a reduction in circulating interleukin-4 and interleukin-5 in atopic asthmatics
Authors: Kosmas EN , Michaelides SA , Polychronaki A , Roussou T , Toukmatzi S , Polychronopoulos V , Baxevanis CN
Published: October 2002

Theophylline, a known phosphodiesterase inhibitor, has been widely used as an additional bronchodilator in asthmatic patients who are not adequately controlled on high-doses of inhaled steroids. However, there is growing evidence that theophylline may also have anti-inflammatory or immunomodulatory effects in asthma. This study investigated whether theophylline administration has an impact on serum levels of interleukin (IL)-4 and IL-5 in asthmatic patients. Eight asymptomatic patients aged 30+/-1.5 yrs (mean +/- SEM) with mild atopic asthma were given a single daily dose of theophylline 150 mg or placebo in an on (theophylline)-off (placebo)-on (theophylline)-off (placebo) protocol with a 3-week duration of each on- or off- interval. Determination of serum IL-4 and IL-5 was done at baseline for all subjects and on the last day of each 3-week interval for the patients under study. Serum IL-4 levels were: 35+/-6 (baseline), 19+/-3 (on-1 interval), 29.5+/-4 (off-2), 15+/-2 (on-3) and 26+/-4 pg x mL(-1) (off-4), while IL-5 levels were 27+/-5, 18+/-4, 28+/-5, 17+/-4 and 28+/-5 pg x mL(-1), respectively. Spirometry was unchanged during the study and serum theophylline levels at the end of the two on-periods were 4.5+/-0.05 and 4.2+/-0.07 microg x mL(-1), while all patients remained asymptomatic. In conclusion, the administration of a low, single, daily dose of oral theophylline in asymptomatic patients with mild atopic asthma seems to reduce circulating interleukin-4 and interleukin-5.
ICAM-1 mediates lung leukocyte recruitment but not pulmonary fibrosis in a murine model of bleomycin-induced lung injury
Authors: Matsuse T , Teramoto S , Katayama H , Sudo E , Ekimoto H , Mitsuhashi H , Uejima Y , Fukuchi Y , Ouchi Y
Published: October 2002

Bleomycin-induced lung injury has been extensively used as a model of interstitial pneumonia and pulmonary fibrosis. Intercellular adhesion molecule (ICAM)-1 is a ligand for lymphocyte function-associated antigen (LFA)-1alpha and has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1alpha pathway in a murine model of bleomycin-induced lung injury. Animals received 75 mg x kg(-1) bleomycin (BLM) i.v. followed by treatment with phosphate-buffered saline (BLM group), anti-ICAM-1 and LFA-1alpha monoclonal antibodies (mAb) (BLM+mAb group). Inflammatory cell counts of bronchoalveolar lavage (BAL) fluid, hydroxyproline content and histological findings were compared between these groups. In the BLM group, significant increases in total cell count, macrophage count and neutrophil count of BAL fluid were observed on days 7 and 14. In the BLM+mAb group, bleomycin-induced accumulation of neutrophils was significantly reduced on days 7 and 14 (p<0.01). However, the administration of mAb to ICAM-1 and LFA-1alpha did not decrease the lung hydroxyproline content or the histopathological fibrosis grading score, indicating that the antagonism of ICAM-I and LFA-1alpha did not attenuate bleomycin-induced pulmonary fibrosis. This study suggests that the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1alpha pathway mediates the accumulation of inflammatory cells in the injured lung caused by bleomycin; however, other mechanisms are important for the subsequent development of pulmonary fibrosis.
Genotype-phenotype correlations in cystic fibrosis: clinical severity of mutation S549R(T-->G)
Authors: Frossard PM , Hertecant J , Bossaert Y , Dawson KP
Published: October 2002

With a view to assessing genotype-to-phenotype correlations in cystic fibrosis (CF), the clinical presentation of CF children from the United Arab Emirates (UAE) who were homozygous for cystic fibrosis transmembrane conductance regulator (CFTR) mutation S549R(T-->G was investigated. This mutation is localized in intron 11 (nucleotide binding domain 1 of the CFTR protein) and had so far been described as a private mutation only. The associations between the R549/R549 genotype and 20 outcome variables, including age at diagnosis, sweat chloride concentrations, growth percentiles, meconium ileus, pancreatic sufficiency, pulmonary disease, associated complications and micro-organism colonization were examined in a group of 15 CF children (9 females and 6 males). Mean current age and age at diagnosis were both low (5.4+/-3.5 and 1.0+/-1.1 yrs, respectively). Although none of the 15 CF patients had presented with meconium ileus at birth, all were pancreatic insufficient and had very severe lung disease, with a high rate of Pseudomonas aeruginosa and Staphylococcus aureus. Two patients died during the course of this investigation (one was 5 months and the other, 6 yrs old). The clinical presentation associated with S549R(T-->G) homozygosity in the United Arab Emirates is quite homogeneous and shows an extreme degree and course of cystic fibrosis severity.
Effect of L-arginine infusion on airway NO in cystic fibrosis and primary ciliary dyskinesia syndrome
Authors: Grasemann H , Gartig SS , Wiesemann HG , Teschler H , Konietzko N , Ratjen F
Published: October 2002

Airway nitric oxide concentrations in patients with cystic fibrosis or primary ciliary dyskinesia syndrome have been shown to be lower than in healthy subjects. Decreased NO concentrations may contribute to impaired ciliary clearance, respiratory tract infections, or obstructive lung disease in these conditions. Nasal and exhaled NO concentrations were compared before and after infusion of 500 mg x kg(-1) L-arginine, the substrate of NO synthases, in 11 cystic fibrosis (CF) patients, seven primary ciliary dyskinesia (PCD) syndrome patients, and 11 control subjects. Baseline nasal and exhaled NO concentrations were significantly lower in both CF and PCD syndrome patients than in controls (p<0.01). In controls, the maximum increase of NO was seen immediately after L-arginine infusion in the upper airways (1.8-fold) and 3 h after the infusion in the lower airways (1.4-fold). Although NO concentrations also increased significantly in both CF (1.9-fold and 1.6-fold, respectively) and PCD syndrome patients (1.4-fold and 1.8-fold, respectively), concentrations remained subnormal compared with baseline values of controls. Pulmonary function remained unchanged in both patient groups. In conclusion, the low airway nitric oxide formation in both cystic fibrosis and primary ciliary dyskinesia syndrome patients can be augmented by L-arginine administration. The finding that pulmonary function remained unchanged in both conditions may be due to the fact that normalization of airway nitric oxide concentrations could not be achieved.
Long-term effectiveness of pulmonary rehabilitation in patients with chronic airway obstruction
Authors: Foglio K , Bianchi L , Bruletti G , Battista L , Pagani M , Ambrosino N
Published: October 2002

The aim of this study was to evaluate the long-term outcome of an outpatient pulmonary rehabilitation programme (PRP) in patients with chronic airway obstruction (CAO). In 61 CAO patients (35 asthmatics and 26 chronic obstructive pulmonary disease (COPD)) lung and respiratory muscle function, exercise tolerance (by symptom limited cycloergometer and walking tests), dyspnoea (Borg scale, visual analogue scale (VAS), baseline and transitional dyspnoea index (BDI and TDI, respectively)) and quality of life (St George's Respiratory Questionnaire (SGRQ)) were assessed at baseline (to), at discharge (t1) and 12 months postdischarge (t2). Preprogramme and post-programme hospital admissions and exacerbations of disease were also recorded. In comparison with baseline, no significant change was observed in lung function tests in either diagnostic group, either at t1 or at t2. In both groups improvements in respiratory muscle strength, exercise tolerance, Borg scale and VAS reported at t1 were partially reduced at t2. Analysis of variance showed that these changes over time were similar in the two groups. Mean values of SGRQ and BDI/TDI improved at t1, and, unlike exercise tolerance, did not worsen at t2. However, a clinically relevant difference in SGRQ between t2 and to was reported only in 56% of asthmatics and 52% of COPD patients. Compared with the preceding 2 yrs, in the year following PRP, hospital admissions and disease exacerbations decreased significantly in both diagnostic groups. Regardless of diagnosis, patients with chronic airway obstruction who underwent an outpatient pulmonary rehabilitation programme maintained an improved quality of life 12 months postdischarge despite a partial loss of the improvement in exercise tolerance.
Endothelin(A)-receptor antagonism attenuates pulmonary hypertension in porcine endotoxin shock
Authors: Wanecek M , Oldner A , Rudehill A , Sollevi A , Alving K , Weitzberg E
Published: October 2002

Porcine endotoxin shock is characterized by pulmonary hypertension, decreased mean arterial pressure and deteriorated cardiac performance. These pathophysiological findings are accompanied by increased plasma endothelin-1 levels. Previous studies have shown that both the pulmonary and systemic circulation are improved by combined endothelinA- and endothelinB-receptor antagonism. This study was designed to evaluate further the specific involvement of the endothelinA-receptor in cardiopulmonary pathophysiology during endotoxin shock. In a porcine endotoxin shock model, the endothelinA-receptor antagonist PD 155080 was administered after the onset of endotoxaemia. Cardiopulmonary vascular changes, dynamic lung compliance, oxygen-related variables and plasma levels of endothelin-1-like immunoreactivity were compared with a control group receiving only endotoxin. PD 155080 counteracted the increase in pulmonary artery pressure seen in control animals. In contrast, cardiac performance was not improved. Dynamic lung compliance was not affected by PD 155080. Plasma levels of endothelin-1-like immunoreactivity increased to a similar degree in both groups. These findings indicate that the endothelin system is involved in the pathophysiology of endotoxin shock. Furthermore, the change in pulmonary circulation seen in the present shock model is to a large extent mediated by the endothelinA-receptor mechanism. In view of previous findings, the deterioration of cardiac performance may involve the endothelinB-receptor, either alone or in combination with the endothelinA-receptor.
The efficacy of a custom-fabricated nasal mask on gas exchange during nasal intermittent positive pressure ventilation
Authors: Tsuboi T , Ohi M , Kita H , Otsuka N , Hirata H , Noguchi T , Chin K , Mishima M , Kuno K
Published: October 2002

Commercially available nasal masks have a large mask volume and give rise to considerable air leaks around the mask during nasal intermittent positive pressure ventilation (NIPPV) which may reduce alveolar ventilation (VA per breath). The effects of a custom-fabricated nasal mask (F-mask) versus a commercially available mask (C-mask) on arterial blood gas measurements, dead space including both physiological and apparatus dead space (VD), air leak and VA per breath were compared in patients with restrictive thoracic disease during short-term NIPPV sessions while using a volume cycled ventilator with equivalent settings for both masks. The mask volume of the C-mask was significantly larger than that of the F-mask (p<0.003). The arterial carbon dioxide tension (Pa,CO2) during NIPPV with either the F-mask (5.56+/-1.35 kPa) (mean+/-SD) or the C-mask (6.87+/-0.96 kPa) was significantly lower than during spontaneous breathing (7.75+/-0.81 kPa; p<0.003), but the Pa,CO2 decreased more during NIPPV with the F-mask than with the C-mask (p<0.003). The VD was significantly smaller (p<0.03), the air leak was significantly less (p<0.03), and the VA per breath was significantly larger (p<0.03) during NIPPV with the F-mask than with the C-mask. In conclusion, nasal intermittent positive pressure ventilation with the F-mask was more effective than nasal intermittent positive pressure ventilation with the commercially available mask due to its smaller dead space and less air leak. Further studies are needed to extend these results to all the commercially available-masks.