bluuebunny/crossref_metadata_2025 huggingface dataset:
Steroid therapy in obstructive airway diseases
Authors: ZAINUDIN BMZ
Published: February 2008

Abstract
Asthma and chronic obstructive pulmonary disease (COPD) are two common illnesses that cause significant morbidity and mortality. Steroids are widely used in both conditions. They act through steroid or glucocorticoid receptors (GR) causing up or down regulation of protein synthesis resulting in an increase in lipocortin 1 and β2 adrenergic receptors, and decreased levels and activities of cytokines or cytokine receptors, which reduces the inflammatory process in the airways and decreases bronchial hyperreactivity. Consequently symptoms of airway obstruction are alleviated and lung function is improved. In asthma, steroids have been convincingly shown to be effective in the treatment of both acute exacerbations and chronic condition. In COPD, however, only a subset of patients seem to respond favourably to steroid therapy. Therapeutic trials are therefore recommended before committing to a long‐term treatment in order to determine this subset of patients, as no markers of steroid responsiveness can be identified. The inhaled steroids currently available have a good safety profile with significant side effects occurring only occasionally. Such side effects are usually confined to the oropharynx, causing local irritation, candidiasis and dysphonia, which can be easily overcome. Biochemical abnormalities involving bone, adrenal, carbohydrate and lipid profiles have been noted with high doses of inhaled steroids; however, these have no significant clinical effects.
Assessment and management of dyspnoea
Authors: JOFFE David , BEREND Norbert
Published: February 2008

Abstract
The terms ‘dyspnoea’ or ‘breathlessness’ refer to an individual's subjective awareness of discomfort related to the act of breathing. Elevations in CO2 above normal levels have been shown to cause breathlessness although it is unlikely to be the sole cause of breathlessness in a clinical setting. Several studies suggest that supplemental O2 during exercise will diminish the sensation of breathlessness although not all work has confirmed this finding. Much about the role of gas exchange in dyspnogenesis remains controversial. Phrenic blockade can abolish dyspnoea in response to breath‐holding, while work in quadriplegics suggests that the intercostal muscles are not involved. A separate and direct pathway from the respiratory centre to the sensory cortex has also be implicated. Threshold discrimination has established that patients with chronic airflow limitation (CAL) have a blunted response to the addition of resistive loads to breathing, while category scaling methods (e.g. the Borg scale) have added descriptive terms to these physiological measures. Questionnaires often appear limited by their subjectivity and lack of correlation with physiological changes, but remain a useful tool in the clinical setting. In regard to therapy of dyspnoea high fat diets have a theoretical advantage in the CAL group but are generally not well tolerated. Resistive training devices and exercise training in CAL have been widely researched but in general, measures of lung remain unaltered and many of the studies would suggest that they have little, if any, inpact on functional status. Beta‐agonists have been widely shown to be useful in CAL patients, despite the fact that bronchodilatation is not always demonstrable. Anticholinergics have be shown to be effective bronchodilators, but whether there is an improvement in dyspnoea above that expected from improvement in lung function is unclear. Animal studies and work in normal individuals would suggest that methylxanthines have a theoretical role in CAL possibly by increasing diaphragmatic muscle strength and decaying fatigue, but toxicity and lack of clear benefit in this group suggest that they should not be used as monotherapy. There is little evidence to support the use of opioids in chronic CAL although their role in the acute dyspnoea of end‐stage CAL remains defined. The use of benzodiazepines has also been disappointing. Bullectomy remains widely accepted in clinical practice. New techniques such as ‘reduction surgery’ for diffuse emphysema are showing promise, although still in need of further testing and validation.
Allergen‐induced airway reactions in atopic asthmatics correlate with allergen‐specific IL‐5 response by BAL cells
Authors: TANG Chibing , ROLLAND Jennifer M. , WARD Christopher , QUAN Baowei , WALTERS E. Haydn
Published: February 2008

Abstract
Allergen‐specific cytokine responses in the airways are thought to play a critical role in the pathogenesis of atopic asthma. This study examined whether there is a quantitative difference in bronchoalveolar lavage (BAL) cell allergen‐induced IL‐5 production between atopic subjects with and without asthma which may relate to a difference in airway response induced by allergen exposure. Twelve atopic asthmatics (AA), nine atopic non‐asthmatics (AN) and 10 normal controls (N) underwent inhalation challenge with house dust mite allergen (HDM) extract. AA differed from AN in having late airway reactions (LAR) after HDM inhalation (P < 0.01), which correlated with an increased percentage of BAL eosinophils and increased BAL cell IL‐5 production after in vivo or in vitro HDM challenge for the AA group (P < 0.01). IL‐5 production by PBMC from both atopic groups was elevated with HDM stimulation in vitro, but AA again had a higher level under baseline conditions than AN (P < 0.02). Furthermore, there was a greater effect of BAL fluid from AA on ECP release by eosinophils compared to that for AN (P < 0.01). These findings suggest that increased IL‐5 production in atopic asthmatic airways contributes to the increased physiological response to allergen inhalation, by modulating local eosinophil recruitment and activation.
Role of platelet activating factor, leukotrienes and polymorphs in the FMLP induced increase in microvascular leakage in rabbit trachea
Authors: MATHESON Melissa J. , RYNELL Anne‐Christine , McCLEAN Melissa A. , BEREND Norbert
Published: February 2008

Abstract
This study was designed to determine the time course of N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP) induced microvascular leakage in the airways of anaesthetized, tracheostomized New Zealand white rabbits. We have previously shown that FMLP increases microvascular leakage in the rabbit trachea at 30 min post challenge. A further aim was to determine the mechanisms underlying this response. Microvascular leakage was assessed using the albumin binding dye, Evans blue which was injected intravenously (50 mg/kg) immediately prior to FMLP challenge (10 mg nebulised for 2 min) or the control (dimethylsulphoxide/saline). Microvascular leakage was assessed in the trachea and bronchi at 15 min, 22.5 min, 45 min and 120 minutes with n=6 for each group. The only significant difference between control and FMLP challenged groups was at 45 min in the bronchi (FMLP 77.6±12.2, control 33.4±5.7, P < 0.05). To determine the mechanism underlying FMLP‐induced increases in microvascular leakage rabbits were treated with one of the following: (i) nitrogen mustard (1.75 mg/kg intravenously), which depletes circulating polymorphs (n=6); (ii) the platelet activating factor (PAF) receptor antagonist WEB 2086 (10 mg/kg; n=5); (iii) the Cys‐LTR1 receptor antagonist ICI198615 (nebulised 10−4 moll L), or challenged with the thromboxane agonist U46619. Tracheal Evans blue concentration was assessed at 30 min after FMLP challenge and compared with the appropriate control. Treatment with WEB 2086 significantly (P < 0.05) reduced tracheal microvascular leakage (FMLP 76.3±13.1 WEB 2086/FMLP 31.4±3.7μg/g trachea) as did ICI 198615 (FMLP 69.8±11.5 ICI198615/FMLP 30.0±5.7). In conclusion FMLP induced an increase in tracheal microvascular leakage which was significant in the bronchi at 45 min and this increase was mediated by platelet activating factor and the sulphidopeptide leukotrienes C4 and D4.
Protein kinase inhibitor attenuates an increase in endothelial monolayer permeability induced by tumour necrosis factor‐α
Authors: YONEMARU Makoto , KASUGA Ikuma , KUSUMOTO Hiroshi , KIYOKAWA Hiroshi , KUWABARA Saburo , ICHINOSE Yuichi , TOYAMA Keisuke
Published: February 2008

Abstract
We questioned the mechanism of the increase in pulmonary endothelial permeability induced by tumour necrosis factor‐α (TNF‐α), a cytokine implicated in the pathogenesis of adult respiratory distress syndrome. As a measure of permeability, we determined the albumin transferred across cultured pulmonary endothelial monolayers prepared on a porous filter. The agents evaluated included protein kinase inhibitors H‐7 and H‐8, a calmodulin antagonist W‐7, and protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and SC‐9. H‐7, more potent in inhibiting PKC than H‐8, failed to attenuate the increase in permeability induced by TNF‐α. Neither PMA nor SC‐9 increased permeability. However, H‐8, which is a potent inhibitor of cyclic nucleotide‐dependent protein kinases, prevented the increase in permeability induced by TNF‐α. These results suggest that protein kinases other than PKC are involved in the signal transduction in endothelial permeability increase induced by TNF‐α. Calmodulin pathway may not be implicated in the increase in permeability induced by TNF‐α.
Hydroxychloroquine therapy of diffuse pulmonary sarcoidosis in two Australian male children
Authors: HILTON Jodi M. , COOPER David M. , HENRY Richard L.
Published: February 2008

AbstractSarcoidosis is a chronic granulomatous disease, seen infrequently in children,1with the capacity to affect multiple systems. The incidence and prevalence of the disease in children is largely unknown but is dependent on many factors including: age, race and geographical location.2There have been very few studies of sarcoidosis in Australian (Aboriginal or white) children. Diffuse pulmonary sarcoidosis is very rare in non‐Scandinavian white Caucasian children, yet in the winter of 1992 two Caucasian males, aged 11.1 and 10.5 years were seen at the John Hunter Hospital in Newcastle. Both boys had pulmonary sarcoidosis and after an initial trial of treatment with steroids responded well to hydroxychloroquine therapy.
Summer‐type hypersensitivity pneumonitis outside Japan: A case report and the state of the art
Authors: YOO Chul‐Gyu , KIM Young Whan , HAN Sung Koo , NAKAGAWA Kazuko , SUGA Moritaka , NISHIURA Yuriko , ANDO Masayuki , SHIM Young‐Soo
Published: February 2008

Abstract
A 61‐year‐old Korean housewife developed dyspnoea, cough and weight loss in the summer of 1994. The case was diagnosed as definite summer‐type hypersensitivity pneumonitis (SHP) according to the criteria proposed for hypersensitivity pneumonitis and for SHP. Her serum antibodies to Trichosporon were positive. Her symptoms were exacerbated after she returned home and Trichosporon was isolated from the patient's home, indicating Trichosporon as the causative antigen. This is the first confirmed case of SHP outside Japan. On the basis of our research in SHP to date, we propose that SHP occurs in other Asian countries and that the assay of anti‐Trichosporon antibodies is useful for the diagnosis of the disease.
Genetic factors in lung disease Part II: Lung cancer and angiotensin converting enzyme gene
Authors: KAWAKAMI Yoshikazu , YAMAGUCHI Etsuro , MUNAKATA Mitsuru , DOSAKA‐AKITA Hirotoshi , FURUYA Ken
Published: February 2008

Abstract
The recent progress in molecular biology has led to the elucidation of pathogenesis of lung cancer. The development of a lung cancer requires multiple genetic changes, consisting of the activation of oncogenes, including the K‐ras and myc genes, and of inactivation of tumour suppressor genes, including the Rb, p53 and CDKN2 genes. Knowing the specific genes undergoing such changes should be useful as biomarkers for the early detection of cells destined to become malignant. Moreover, such genetic changes could be targets of newly designed drugs and gene‐based therapy. Although the angiotensin I‐converting enzyme was originally discovered in equine plasma, it has been recognized in various organs and cells other than vascular endothelial cells. This enzyme is also known to have wide substrate specificity to many peptides. The definite roles of angiotensin converting enzyme (ACE) in the respiratory system are largely unknown. Recent progress in molecular biology of the ACE, however, gives us a good chance to look over the significance of ACE in respiratory diseases as well as cardiovascular disorders. In this review, we show the recent advances in the basic studies of the ACE and refer to its clinical application.
The proteinase–antiproteinase theory of emphysema: A speculative analysis of recent advances into the pathogenesis of emphysema
Authors: KNIGHT Kenneth R , BURDON Jonathan GW , COOK Luisa , BRENTON Sue , AYAD Monna , JANUS Edward D
Published: February 2008

Abstract
This review concerns the reasons why only an estimated 10–15% of patients with alpha‐1‐antitrypsin (A1AT) deficiency develop the destructive lung disease known as emphysema. The arguments presented revolve around the proteinase‐antiproteinase balance in the ‘micro‐environment’ of the epithelial space of the lung. Attention is focused on the balance between destructive enzymes such as neutrophil elastase and protective proteins such as A1AT, secretory leucocyte proteinase inhibitor (SLPI), human elastase inhibitor (HEI) and elafin. When neutrophil elastase is already attached to the elastin fibres the smaller molecules SLPI and elafin appear to be better inhibitors of this enzyme than larger inhibitors such as A1AT and HEI. Furthermore, SLPI and elafin may provide the first line of defence against proteinase attack from neutrophil elastase. In trying to explain the variability in the clinical expression of A1AT‐deficiency and the development of emphysema, the importance of changes to A1AT, SLPI and elafin molecules induced by smoking and/or oxygen free radicals has been considered. It is possible that emphysema only develops in patients who have SLPI/elafin deficiency as well as A1AT deficiency.
Testing airway responsiveness using inhaled methacholine or histamine
Authors: JAMES Alan , RYAN Gerard
Published: February 2008

Abstract
Airway responsiveness assessed using histamine and methacholine is safe, reproducible and relatively easily undertaken in adults and children. Results are similar for methacholine and histamine although methacholine is better tolerated. Responsiveness is increased in children and the elderly, and in women compared to men, possibly due to body size effects. Baseline lung function confounds the interpretation of airway responsiveness and may explain the effect of smoking in most studies. Results are most usefully expressed as the provocative dose producing a 20% fall in FEV1 (PD20FEV1) or the dose‐response slope (DRS). When technical factors are controlled the reproducibility of the test is from one to two doubling doses. Measurements of airway responsiveness have been widely used in clinical and research practice. However, assessing their value in diagnosing asthma is limited by the lack of a gold standard for the definition of asthma. Using a cut‐off value of 8 mg/mL or 8 μmol for PD20, the tests will discriminate asthmatic from non‐asthmatic subjects (based on questionnaire definitions of asthma) with a sensitivity of around 60% and a specificity of around 90%. These properties of the test result in positive and negative predictive values of 86% and 69% when the prevalence of asthma is high (50%– as in the clinical setting) and 40% and 95% when the prevalence of asthma is low (10%, as in general population studies). In the usual clinical setting, assessing the significance of atypical or non‐specific symptoms, the tests are of intermediate value in predicting the presence of asthma and less useful in excluding asthma. The additional benefit of testing airway responsiveness to measuring peak flows or to a trial of therapy has yet to be fully assessed. Testing of airway responsiveness may be of value in assessing occupational asthma, asthma severity and the effects of potential sensitizers or treatments. In research, tests of airway responsiveness are more useful for excluding cases of asthma. In population studies, they serve as an objective marker of abnormal airway function which may be genetically determined and, like allergy, are strongly associated with asthma. The predictive value of airway hyperresponsiveness for the development of airway disease is yet to be clearly established. In epidemiology the benefits of measuring airway responses must be weighed against the added inconvenience and cost that is incurred.
Pulmonary dysanapsis, methacholine airway responsiveness and sensitization to airborne antigen
Authors: MUNAKATA Mitsuru , OHE Masashi , HOMMA Yukihiko , KAWAKAMI Yoshikazu
Published: February 2008

Abstract
Whether the disproportional growth of airways relative to lung parenchyma (dysanapsis) has any relationship to the development of non‐specific bronchial hyperresponsiveness and atopy was investigated in 45 family members of the patients with atopic asthma. As indices of pulmonary dysanapsis, forced expiratory flow25‐75/forced vital capacity (FEF25‐75/FVC) and the tracheal cross sectional area divided by the forced expiratory volume (X‐SA/FVC) were examined. As an index of non‐specific airway responsiveness, the cumulative dose of inhaled methacholine needed to induce 35% reduction of respiratory conductance (PD35) was determined by continuous respiratory resistance measurement. For examination of atopy, skin prick tests were conducted, and total serum IgE and IgE specific to common inhaled antigens were measured. FEF25‐75/FVC showed no significant correlation to FVC but showed a significant correlation to log (PD35). When the analysis was done in the subjects whose FEVI/FVC was more than 0.8, FEF25‐75/FVC showed a significant negative correlation to FVC but lost its correlation to log(PD35). X‐SA/FVC showed a significant negative correlation to FVC but had no significant correlation to log(PD35). These relations were conserved when the analysis was done in subjects without airway obstruction. In addition, FEV1/FVC had a significant correlation to log(PD35) and FEF25‐75/FVC. However, subjects who had a positive IgE(MAST) had a significantly smaller X‐SA/FVC than those with a negative IgE(MAST) (0.60 ± 0.14[SD] and 0.72 ± 0.18, respectively, P<0.02). These results suggest that although pulmonary dysanapsis does not have a significant relation to airway responsiveness to inhaled methacholine, it may be associated with sensitization to airborne antigens.
Effects of pulmonary surfactant on macrophage migration: Suppression of chemokinesis by surfactant phospholipid and enhancement of chemotaxis by surfactant protein
Authors: TANAKA Fujiho , SUGA Moritaka , NISHIKAWA Hiroshi , MURANAKA Hiroyuki , ANDO Masayuki
Published: February 2008

Abstract
We fractionated the bronchoalveolar lavage fluid (BALF) from normal rabbit lungs into several fractions by high speed centrifugation and ethanol‐ether extraction. Random migration, chemokinesis and chemotaxis of freshly harvested alveolar macrophages (AM), 24 h cultured AM, and peritoneal exudate cells (PEC) were assayed in vitro using a modified, under agarose method and a blind well chemotactic chamber method. Freshly harvested AM demonstrated little random migration compared with PEC. However, when freshly harvested AM were pre‐incubated in surfactant free medium for 24 h, the cells showed the same rate of migration as PEC. The increased migration of the 24 h cultured AM was partially suppressed by the presence of all BALF fractions containing high proportions of phospholipid. The inhibition by Fr‐L (a fraction enriched in phospholipids) was reversed by normal serum, but not by heat‐inactivated serum, cholesterol, synthetic dipalmitoyl phosphatidyl choline, or indomethacin. Fr‐L markedly suppressed macrophage chemokinesis but did not affect on macrophage chemotaxis. Alternatively, Fr‐P, a delipidated preparation of surfactant consisting mainly of protein, had no effect on macrophage chemokinesis but increased the chemotaxis of PEC to zymosan‐activated serum. We conclude that surfactant phospholipid suppresses AM migration, while surfactant protein increases macrophage chemotaxis.
Surgical results of 23 patients with tracheobronchial injuries
Authors: WU Ming‐Ho , TSENG Yau‐Lin , LIN Mu‐Yen , LAI Wu‐Wei
Published: February 2008

Abstract
The objective of this study was to evaluate the surgical results of tracheobronchial injuries. Between July 1988 and March 1996, tracheobronchial surgery was performed on 23 injured patients. According to the aetiology, the injuries were categorized as blunt injury (n= 13), cutting or penetrating injury (n= 5), and corrosive injury (n= 5). Blunt injuries included three complete laryngotracheal disruptions, one tracheal laceration, and eight bronchial ruptures. Cutting or penetration injuries included four laryngotracheal ruptures and one tracheal cutting wound. Corrosive injuries included one tracheal necrosis, one tracheal stenosis and three esophago‐ respiratory fistulae. Operative procedures that were performed on the tracheobronchus included tracheoplasty (n= 12), bronchoplasty (n= 7), sleeve resection of the trachea (n= 2) and bronchus (n= 2). Two hospital deaths were encountered, with a mortality rate of 8.7%. One patient with caustic injuiy died of bronchopleural fistula and empyema. The other patient died with multiple injuries from multiple organ failure which was unrelated to the bronchoplasty. One postoperative complication was restenosis of the trachea in a caustic injured patient, which was treated by a T‐tube insertion. In conclusion, tracheobronchoplasty is an effective life‐saving emergency procedure for the patients with tracheobronchial injuries.
Nasal mask continuous positive airway pressure in the treatment of chronic nocturnal cough in a young child
Authors: TENG Arthur Y , SULLIVAN Colin E
Published: February 2008

Abstract
The objective of this case report was to define the effects of nasal mask continuous positive airway pressure (CPAP) on the respiratory and sleep characteristics of a 3 year‐old boy with a 2 year history of snoring and 1 year history of chronic nocturnal cough. The method employed was all‐night polysomnography before and during treatment with CPAP after the identification of partial upper airway obstruction in association with cough. The results indicated that the child had evidence of mild upper airways obstruction on initial all‐night sleep study. Nasal mask CPAP was instituted. On a subsequent sleep study 4 weeks later, this was documented to prevent the upper airway obstruction at a pressure of 5.2 cm of water. In addition, nasal mask CPAP markedly reduced the nocturnal coughing, the total number of coughs decreasing from 92 to one. The rate of cough per h of study (cough disturbance index) decreased from 9.8—0.1. Sleep efficiency (total sleep time as a percentage of study duration) improved on CPAP from 87 to 99%. This study suggests that chronic nocturnal cough can result from upper airway obstruction in sleep in children and is an important initial observation.
Multiple pulmonary nodules after recovery from chickenpox in a patient with chronic lymphocytic leukaemia
Authors: MIYASHITA Yoshihiro , KOIKE Hiroaki , MISAWA Akihiko , SHIMIZU Hideaki , YOSHIDA Kazunori , YASUTOMI Takashi , KANAI Nobuyuki , KAGAMI Toshihide
Published: February 2008

Abstract
A 61‐year‐old woman with chronic lymphocytic leukaemia (CLL) was found to have multiple pulmonary nodules on an annual chest radiograph 4 months after recovery from chickenpox. To exclude the metastatic carcinoma, an open lung biopsy was performed. Histological examination disclosed isolated necrotic nodules surrounded by some lymphocytes and a few giant cells. These histological findings were compatible with healed varicella pneumonia and the DNA of varicella‐zoster virus (VZV) was detected by polymerase chain reaction (PCR) method. We report a case of asymptomatic pulmonary involvement of VZV infection in a patient with CLL.
Population based standards for pulmonary function in non‐smoking adults in Singapore
Authors: CHIN NK , NG TP , HUI KP , TAN Wan C
Published: February 2008

Abstract
Ethnic differences in lung function are well recognized, hence the use of normative data should therefore be based on reference equations that are derived specifically for different ethnic groups. We have collected data (n=406) for population‐based reference values of lung function from randomly selected samples of healthy non‐smoking adults of both gender (aged 20–79 years) for each of the three major ethnic groups (Chinese, Malay and Indians) in Singapore. Lung function forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, diffusion capacity (transfer factor) for carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV), RV/TLC and functional residual capacity (FRC) was measured using standardization procedures and acceptability criteria recommended by the American Thoracic Society. Lung function values were predicted from age, height, weight, body mass index (BMI) and transformed variables of these anthropometric measures, using multiple regression techniques. Ethnic differences were demonstrated, with Chinese having the largest lung volumes and flow rates, and Indians the smallest. These prediction equations provide improved and additional (TLC, RV, RV/TLC, FRC) population‐based reference values for assessment of pulmonary health and disease in Singapore
Ameliorating effect of erythromycin on bleomycin‐induced pulmonary fibrosis: Role of alveolar macrophage activation and cytokine release
Authors: CHEN Baiyn , JIANG L , ZHAO W , YU R , HOU XM
Published: February 2008

Abstract
The objective of this study was to evaluate the effectiveness of erythromycin (EM) on bleomycin‐induced pulmonary fibrosis in rats and its possible mechanisms. Seventy‐five rats were divided into three groups. Alveolar macrophages (AM) were harvested through bronchalveolar lavage (BAL) and consecutive changes of tumour necrosis factor‐α (TNF‐α) and platelet‐derived growth factor (PDGF) in AM supernatant and bronchoalveolar lavage fluid (BALF) were assayed with ELISA and bioassay, respectively. The AM‐derived TNF‐α was elevated on day 3, peaked day 7 and then decreased but remained at higher level until day 28. The AM‐derived PDGF was increased on day 3, peaked on day 7 then decreased to non‐statistically significant higher level. The TNF‐α in BALF was increased significantly on day 3 then decreased to normal level; the peak preceded that of AM‐derived TNF‐α. The PDGF in BALF was increased on day 3, peaked on day 7, and then decreased to normal, which exhibited a consecutive change similar to that of AM‐derived PDGF. The EM significantly suppressed TNF‐α and PDGF release by AM, markedly decreased TNF‐α and PDGF levels in BALF. The EM also lessened the collagen deposition, the lung hydroxyproline comprised 75.44%, 72.72% and 56.24% that of bleomycin‐treated group on day 7, 14 and 28, respectively. In conclusion, EM can ameliorate bleomycin‐induced pulmonary fibrosis possibly through suppression of TNF‐α and PDGF as well as the inhibition on accumulation of inflammatory cells in the lung.
Carbon dioxide recruitment threshold as a predictor of successful weaning in chronic obstructive pulmonary disease patients: A pilot study
Authors: KOH Abner T , de GUIA Teresita S , ANG Evelyn T
Published: February 2008

Abstract
Several methods have been used to predict successful weaning and extubation among chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to determine whether carbon dioxide recruitment threshold (PCO2RT) can be used as adjunct to conventional weaning parameters to predict early weaning and successful extubation. Twelve COPD patients who were ready to be extubated based on conventional weaning parameters were divided into group A (n= 7) and group B (n= 5). Group A were those patients with better weaning parameters and hence a higher probability of successful extubation as compared to group B. Carbon dioxide apnoeic threshold (PCO2AT) was obtained by hyperventilating the patient using an increment of two breaths per min until apnoea occurs. At this point, the PCO2AT or the PaCO2 during said apnoeic period was recorded. A dead space of 150 cc is then added to the circuit until the patient starts to breathe as evidenced by the sensitivity trigger indicator. The PCO2 obtained at this period is termed PCO2RT. After weaning for 30 min on a T‐tube, another arterial blood gas is determined and this is called the PCO2SB or the CO2 level after 30 min on spontaneous breathing. If the PCO2SB‐PCO2RT difference is high with a sensitivity of 85.71% and specificity of 100% vs sensitivity of 57.14% and specificity of 60% using the conventional weaning parameters. Thus an increase in PCO2SB at 30 min T‐tube is indicative of impending respiratory pump failure and that other causes of failure to wean must be investigated.
Gastro‐oesophageal reflux disease and asthma
Authors: CHOY Dominic , LEUNG Roland
Published: February 2008

Abstract
Gastro‐oesophageal reflux disease (GOR) and asthma are both common medical conditions that often co‐exist. Studies using oesophageal manometry and 24 h ambulatory pH monitoring have shown that up to 80% of asthmatics have abnormal GOR. A number of mechanisms whereby GOR may trigger asthma have been proposed, and it is believed that acid reflux may stimulate vagal receptors in the lower oesophagus causing reflex bronchoconstriction. However, GOR may be worsened by asthma causing abnormal diaphragm mechanics and by its treatment. Formal evaluation of GOR should be considered a part of asthma assessment, particularly if asthmatic symptoms are precipitated by factors known to trigger GOR such as reclining, alcohol ingestion, and the use of theophylline. Twenty‐four hour ambulatory intra‐oesophageal pH monitoring remains the gold standard for the diagnosis of GOR. Medical therapy with anti‐refux medications, such as acid suppressive agents and prokinetic agents may improve both GOR and asthma control. In those who fail medical therapy, anti–reflux surgery may be warranted in some.
Environment and the ageing lung*
Authors: BOVORNKITTI Somchal , LIMLOMWONGSE Liangchai
Published: February 2008

Abstract
A brief review of changes in the morphology, physiology and defence mechanism in the ageing lung is presented. During the ageing process, the lung is also affected by environmental insults, which can be exogenous or endogenous. Exogenous factors include infection, climate, air pollution and mechanical injuries, whereas endogenous environments are certain system diseases (e.g. diabetes mellitus and thromboembolism) as well as infectious diseases (e.g. tuberculosis).
Non‐invasive ventilation in the management of respiratory failure
Authors: Chan Joseph KW , Leung Roland CC , Lai Christopher KW
Published: February 2008

Abstract
Non‐invasive positive pressure ventilation (NIPPV) has been used increasingly to treat various forms of respiratory failure, with benefits in terms of gas exchange improvement, avoidance of endotracheal intubation and a decreased mortality. This review will focus on the recent developments and recommendations in the use of NIPPV in the treatment of acute and chronic respiratory failure, the methodology in the application of NIPPY, and briefly on its proposed mechanism of action.
Surgical results of 29 patients with benign tracheobronchial lesions
Authors: WU Ming‐Ho , TSENG Yau‐Lin , LIN Mu‐Yen , LAI Wu‐Wei
Published: February 2008

Abstract
This study was carried out in order to evaluate the surgical results of benign tracheobronchial diseases. Between July 1988 and March 1996, tracheobronchial surgery was performed on 29 patients with a variety of benign diseases. The primary diseases were post intubation or post tracheostomy tracheal stenosis (n= 12), tuberculous stenosis (n= 7), congenital tracheal stenosis with or without vascular ring (n= 4), tracheobronchial tumour (n= 2), oesophageal tumour (n= 1), and miscellaneous conditions (n= 3). Thirty‐one operative procedures included sleeve lobectomy (n= 7), sleeve resection of trachea (n= 17) and bronchus (n= 2), and plastic surgery of trachea (n= 4) and bronchus (n= 1). There was one operative death, which put the mortality rate at 3.4%. There were five postoperative complications in this series (17.2%), including anastomotic disruption of trachea (n= 1), bilateral vocal cord palsy (n= 1), prolonged endotracheal intubation (n=1) and overgrowth of granulation (n= 2). The complication of anastomotic disruption of trachea was treated by insertion of a tracheal T‐tube, and the granulation was treated by bronchoscopic excision. We suggest that tracheobronchoplasty is a safe procedure in carefully selected patients with benign diseases.
Hepatocyte growth factor promotes growth and lumen formation of fetal lung epithelial cells in primary culture
Authors: SATO Noboru , TAKAHASHI Hideki
Published: February 2008

Abstract
Mesenchyme‐epithelium interactions are generally considered critical for fetal lung development. Hepatocyte growth factor (HGF), a mesenchyme‐derived mitogen active on a variety of epithelial cells, appears to be involved in the morphogenesis of fetal liver and kidney. During lung development, HGF and its receptor, c‐Met, are expressed in close proximity in mesenchymal cells and epithelial cells, respectively. To examine the role of HGF in fetal lung development, we investigated the effects of HGF on lung epithelial cells derived from a 15‐day‐old mouse fetus. First, HGF induces a 45% increase in [3H]thymidine incorporation and a 65% increase in cell number by crystal violet analysis at 10 ng/mL concentration, and the increase is dose dependent. Second, HGF facilitates the formation of an organotypic arrangement of the fetal epithelial cells on a basement membrane extract (Matrigel) that resembles alveolar structures in vivo, and the maximum increase is about twice the control level at 10 ng/mL. These results suggest that HGF may be implicated in fetal lung development through the regulation of mesenchyme‐epithelium interactions.
Tachykinins contribute to the acute airways response to allergen in sheep actively sensitized to Ascaris suum
Authors: REYNOLDS Paul N , RICE Anthony J , REYNOLDS Ann M , THORNTON Andrew T , HOLMES Mark D , SCICCHITANO Raffaele
Published: February 2008

Abstract
Tachykinins, found in sensory nerves, have effects in the airways which suggest that they may contribute to the pathogenesis of asthma. We aimed to find evidence for tachykinin involvement in the immediate airway response to allergen in a sheep model of experimental asthma. Twenty‐four sheep were actively sensitized to Ascaris suum, then challenged with nebulized Ascaris extract in a dose‐response fashion. Change in lung resistance (RL) in response to challenge was measured. Responder sheep (those with an increase in RL of >100% over baseline) that had reproducible responses over three challenges were identified (n= 4 sheep) and a PC100 (number of breaths of extract required to induce a 100% increase in RL) was determined. The effect of the neutral endopeptidase inhibitor phosphoramidon, the NK‐1 receptor‐specific antagonist CP 96, 345 and capsaicin desensitization on the RL response to Ascaris challenge was then assessed. Administration of phosphoramidon before Ascaris decreased the PC100 to 31 ± 7% of the PC100 seen with Ascaris alone (P<0.05), whereas CP 96,345 and capsaicin desensitization increased the PC100 to 285 ± 41% and 555 ± 93% respectively (P<0.05 for both). These findings suggest that endogenous tachykinins are released in response to allergen challenge and that they contribute to the immediate increase in RL.
A case of malignant pleural mesothelioma following exposure to atomic radiation in Nagasaki
Authors: MIZUKI Masami , YUKISHIGE Keiko , ABE Yasuharu , TSUDA Tomiyasu
Published: February 2008

Abstract
We report the case of a 75‐year‐old Japanese man who developed malignant mesothelioma in the left hemithorax 50 years after the dropping of the atomic bomb on Nagasaki in 1945. This may be the first reported case of malignant mesothelioma following exposure to atomic radiation. Asbestos is the leading cause of malignant mesothelioma, but radiation therapy is the primary non‐asbestos‐related cause. In the case of radiation therapy, the interval between exposure and the occurrence of malignant mesothelioma tends to be many years. This patient was at a high risk of malignant mesothelioma as he had been exposed to radiation from the atomic bomb and may also have had a history of asbestos exposure at the munitions factory where he was employed as a shipbuilder for 2 years. It has been suggested that combined exposure to atomic radiation and asbestos is associated with an increased incidence of malignant mesothelioma. If thickening of the pleura or pleural effusion is found in atomic bomb survivors, malignant mesothelioma should be considered as one of the options in the differential diagnosis, even although the atomic bomb attacks occurred several decades ago.
Tuberculosis and HIV Infection: Global Perspectives
Authors: Murray John F
Published: February 2008

Abstract
This paper reviews the epidemiological and clinical aspects of the interaction between Mycobacterium tuberculosis and HIV infection. The incidence of HIV‐associated tuberculosis is increasing worldwide and is expected to increase further, especially in Africa and parts of Asia. HIV infection appears to increase the likelihood that tuberculous infection will occur after tubercle bacilli are inhaled into the lungs. Moreover, there is persuasive evidence that in the presence of HIV infection, new‐onset tuberculous infection will progress rapidly to clinically significant disease and the probability that latent tuberculous infection will reactivate is enormously increased. The accelerating and amplifying influence of HIV infection is also contributing to the increasing incidence of disease caused by multidrug‐resistant strains of M. tuberculosis. Neither clinical nor radiographic features reliably distinguish the majority of patients with HIV‐associated tuberculosis from those who are non‐HIV‐infected. Some HIV‐infected patients, however, have atypical manifestations and are difficult to diagnose. Chemotherapy for 6 months with conventional antituberculosis drugs cures most patients, but many died during or after treatment of other AIDS‐related complications. HIV is contributing heavily to the worldwide increase in tuberculosis. There is also mounting evidence that tuberculosis accelerates the course of co‐existing HIV disease.
Current issues in the management of chronic obstructive pulmonary diseases
Authors: ROCHE N , HUCHON GÉRALD J
Published: February 2008

Abstract
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, especially among smokers. Many guidelines that have recently been issued emphasize that COPD is not inaccessible to therapeutic measures: although few interventions are capable of affecting its natural history (i.e. smoking cessation and, in patients with severe resting hypoxaemia, oxygen therapy), several others have a demonstrated effect on symptoms and, antitrypsin replacement therapy in emphysema due to alpha1‐antitrypsin deficiency are currently being studied. When there is a marked increase in mucus production, chest physiotherapy using controlled expiration and directed cough maybe useful. Inhaled bronchodilators are frequently effective on dyspnoea, anticholinergic agents being more suitable for continuous symptoms. Rehabilitation, which includes education and psychosocial care, chest physiotherapy, nutritional care and exercise training, also improves quality of life. When there is persistent severe alveolar hypoventilation despite oxygen therapy, long‐term mechanical ventilation may be considered. Surgical options in the treatment of emphysema include resection of giant bullae and lung volume reduction surgery. Lung transplantation should be proposed only in patients with end‐stage disease, the difficulty here being to define what ‘end‐stage’ means. Finally, all preventive and some therapeutic interventions are likely to be more effective early in the course of the disease. Thus, efforts should be made to detect airways obstruction early in subjects at risk, such as smokers.
Applications of colour Doppler ultrasound in the diagnosis of chest diseases
Authors: YANG Pan‐Chyr
Published: February 2008

Abstract
Colour Doppler ultrasound (US) or colour Doppler imaging is a new imaging modality that can simultaneously display blood flow information and Doppler spectral analysis. This new technique provides an opportunity to assess pulmonary blood flow and perfusion non‐invasively. Colour Doppler US has many potential applications in diseases of the chest. Colour Doppler imaging is useful in assisting the diagnosis of pulmonary arteriovenous malformation and pulmonary sequestration. The ‘fluid colour sign’ can be used to detect minimal effusion amenable to thoracentesis. Colour Doppler US can be used to assess the angiogenesis of a lung tumour and may be helpful in differentiating a malignant tumour from a benign one. Colour Doppler US can be used to guide a transthoracic needle biopsy and improve the safety of this invasive procedure. Colour Doppler US can demonstrate the vascular patterns and assess the regional haemodynamic changes of a pulmonary consolidation. The information of spectral wave analysis is helpful for understanding the haemodynamic changes of a pulmonary consolidation. Colour Doppler US is useful in assessing perfusion and reperfusion status of a pulmonary infarction. The recent advent of amplitude US angiography further improved the sensitivity of colour Doppler US in detecting blood flow signal without angle restriction. The potential applications of these new techniques in chest diseases may need further exploration.
Central sleep apnoea and heart failure (Part I)
Authors: BURGESS Keith R
Published: February 2008

Abstract
Central sleep apnoea (CSA) in congestive heart failure is sleep state dependent and occurs typically in stages I and II of non‐REM sleep. The pre‐requisites are hypocapnia and some prolongation of the circulation time. It is not certain whether abnormalities in after‐discharge activity in the brainstem are also important. The presence of CSA in patients with left ventricular dysfunction is a poor prognostic sign and associated with a higher mortality in that group compared to age, sex and ejection fraction matched patients with congestive cardiac failure alone. It is reasonable to speculate that the CSA causes an increase in sympathetic nervous system activity which would maintain afterload at a high level or tend to increase it with time. The application of a high afterload to an impaired left ventricle leads over time to a further reduction in ejection fraction. From other studies, particularly ACE inhibitor studies, it is known that ejection fraction and prognosis are almost linearly related. It could therefore be said that once CSA has developed it may lead to a vicious circle of increasing afterload and further reduction in ejection fraction, causing worsening CSA and further increases in afterload. A number of treatments have been shown to be of benefit: supplemental nocturnal oxygen therapy, acetazolamide and nasal CPAP therapy have all been shown to reduce CSA. In addition nasal continuous positive airways pressure (CPAP) has been shown by two groups in Canada to also improve ejection fraction. The beneficial effects on ejection fraction in particular, persist after the treatment has been withdrawn, which suggests either remodelling of the left ventricular musculature or a resetting of the baseline sympathetic nervous system activity. The impressive increase in ejection fraction due to three months nasal CPAP therapy in one study (an average 35% increase) is both dramatic and exciting for the future. It is reasonable to expect improvement in prognosis for patients with CCF whose ejection fraction rises with CPAP treatment. Finally, only a limited number of studies have been published. Unfortunately the impressive results from Canada have not yet been reproduced in other centres around the world.
The effects of a specific tachykinin receptor antagonist FK‐224 on ozone‐induced airway hyperresponsiveness and inflammation
Authors: AIZAWA H , KOTO H , NAKANO H , INOUE H , MATSUMOTO K , TAKATA S , SHIGYO M , HARA N
Published: February 2008

Abstract
We have demonstrated previously that tachykinin depletion by capsaicin prevented the ozone‐induced airway hyperresponsiveness and the bronchial wall oedema in guinea pigs. To further clarify the role of neurogenic inflammation in ozone‐induced airway hyperresponsiveness, we investigated the effects of a specific tachykinin receptor antagonist (FK‐224) in guinea pigs. Animals were anaesthetized, tracheostomized and mechanically ventilated. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and box flow in a plethysmograph. Airway responsiveness was assessed by determining the provocative concentration of histamine aerosol that increased RL to twice the baseline value (PC200). Animals were injected with either FK‐224 (10 mg/kg, dissolved in 0.2 mL/kg DMSO) or vehicle (0.2 mL/kg DMSO) intravenously, then pre‐ozone PC200 was determined. Following this measurement, animals were exposed to 3 ppm ozone for 60 min. Immediately after exposure, the histamine dose response curve was evaluated again. Bronchoalveolar lavage (BAL) was performed in animals treated with FK‐224 or vehicle. In animals treated with vehicle, ozone exposure caused significant decrease in PC200 and moderate increase in neutrophils in BAL fluid. FK‐224 pre‐treatment significantly inhibited ozone‐induced hyperresponsiveness. Neutrophils in BAL fluid did not significantly increase after ozone exposure in animals treated with FK‐224. By contrast, the degree of epithelial desquamation did not differ significantly between the two groups. We conclude that neurogenic inflammation caused by tachykinin release may be responsible for ozone‐induced bronchial hyperresponsiveness, and that tachykinins may play a role in the initiation of airway inflammation.
Role of sensory innervation and mast cells in neurogenic plasma protein exudation into the airway lumen
Authors: KOWALSKI Marek L , DIDIER Alain , Lundgren Jens D , IGARASHI Yasushi , KALINER Michael A
Published: February 2008

Abstract
Neurogenic inflammation in the airways involves both mucosal oedema and plasma protein exudation into the airway lumen. We aimed to investigate the mechanism of exudation of plasma proteins into the airway lumen. Neurogenic inflammation was induced in anaesthetized Sprague‐Dawley rats by electrical stimulation of both vagal nerves at 20 V, 10 Hz, 5 ms. Vascular permeability was measured as 125I‐albumin extravasation into both the airway wall and tracheobronchial lavage fluid. Following vagal stimulation, tracheobronchial lavages were analysed for albumin, total protein, histamine, immunoreactive substance P (SP), and immunoreactive calcitonin gene‐related peptide (CGRP). Vagal stimulation rapidly increased vascular permeability in the airway mucosa and induced exudation of plasma proteins into the tracheobronchial fluid. Pretreatment with capsaicin inhibited both neurogenic vascular permeability and movement of albumin into the airway lumen. SP and CGRP were detectable in basal lavages (1.37 ± 0.12 ng/mL and 2.17 ± 0.21 ng/mL, respectively) and the concentration of SP fell by 43% following treatment with capsaicin. Following vagal stimulation, concentrations of both SP and CGRP decreased significantly. Although basal tracheobronchial lavages contained histamine, vagal stimulation did not increase the histamine concentration. These results indicate that both neurogenic vascular permeability and plasma protein exudation into the airway lumen results from activation of capsaicin‐sensitive sensory nerves and the reaction is not associated with mast cell activation.