bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats
Authors: Pison CM , Chauvin C , Perrault H , Schwebel C , Lafond JL , Boujet C , Leverve XM
Published: November 2002

Hypoxia is well known to affect carbohydrate metabolism through its action on liver function and thus on glucose homeostasis. The aim of this study was to examine the carbohydrate, lipid and protein metabolic responses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to standardize for the marked hypophagia observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2% in controls, p<0.001). Hypoxia plus fasting led to a significant increase in plasma glucose, lactate, insulin and catecholamine concentrations, while the increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptation to fasting, from gene expression to weight loss. Since hypoxaemia associated with fasting has detrimental effects on nutritional balance, the present observations may be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.
Mouth occlusion pressure, CO2 response and hypercapnia in severe chronic obstructive pulmonary disease
Authors: Montes de Oca M , Celli BR
Published: November 2002

The resting mouth occlusion pressure 0.1 s after onset of inspiration (P0.1) and minute ventilation (V'E) and their response to CO2 in patients with chronic obstructive pulmonary disease (COPD) remain controversial. The ventilatory drive and the factors that predict resting arterial CO2 tension (Pa,CO2) were studied in 19 eucapnic and 14 hypercapnic severe COPD patients, and 20 controls. The CO2 response was evaluated by the Read technique. The V'E, and P0.1 as a function of end-tidal CO2 tension (Pet,CO2) was used to study the ventilatory (deltaV'E/deltaPet,CO2) and P0.1 response (deltaP0.1/deltaPet,CO2). In the patients, respiratory muscle function and pleural occlusion pressure 0.1 s after onset of inspiration (Ppl,0.1) were evaluated with simultaneous measurement of pleural (Ppl) and gastric (Pga) pressures. Hypercapnic patients had lower forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and arterial O2 tension (Pa,O2). Resting P0.1 was higher in patients than in controls, whereas deltaP0.1/deltaPet,CO2 was similar in the three groups. There was no difference in resting P0.1 (3.6+/-2.0 versus 4.3+/-2.8 kPa (2.7+/-1.5 versus 3.2+/-2.1 cmH2O), p=0.2) and Ppl,0.1 (1.4+/-2.3 versus 5.2+/-3.3 kPa (4.08+/-1.7 versus 3.9+/-2.5 cmH2O), p=0.22) between eucapnic and hypercapnic COPD, whereas deltaV'E/deltaPet,CO2 was lower in the hypercapnic group (0.29+/-0.24 versus 0.66+/-0.5 L x min(-1) x kPa, p<0.001). By logistic regression only FEVI and increased diaphragmatic load, and not respiratory drive, predicted resting Pa,CO2. Irrespective of CO2 level, baseline central drive (represented by the mouth occlusion and pleural pressures) and CO2 response are preserved in most patients with severe chronic obstructive pulmonary disease. Effective ventilation is inadequate in the more severely obstructed patients and this results in hypercapnia. Neuroventilatory coupling failure is an attractive explanation for chronic hypercapnia in these patients.
Use of mouth pressure twitches induced by cervical magnetic stimulation to assess voluntary activation of the diaphragm
Authors: de Bruin PF , Watson RA , Khalil N , Pride NB
Published: November 2002

There is a need for a simple method to assess the adequacy of diaphragm activation during voluntary inspiratory efforts in patients with suspected respiratory muscle weakness. We have compared mouth (Pmo,t), oesophageal (Poes,t) and transdiaphragmatic (Pdi,t) twitch pressure elicited by cervical magnetic stimulation (CMS) in five normal men (mean (SD) age 32.2 (1.8) yrs) on two separate study days. Single magnetic stimuli were delivered at functional residual capacity during relaxation and during graded voluntary inspiratory efforts against a closed airway. As voluntary-effort transdiaphragmatic and oesophageal pressure increased, Pdi,t and Poes,t decreased linearly (r range, respectively, 0.82-0.98 and 0.87-0.95). During relaxation, Pmo,t was unreliable due to the poor transmission of intrathoracic pressure, but during inspiratory efforts, the relation between voluntary mouth pressure and Pmo,t was also linear (r range 0.84-0.95). On average, our subjects voluntarily generated 99, 100 and 102% of the maximum transdiaphragmatic, oesophageal and mouth pressures predicted by the respective linear regression equations. Pmo,t was correlated to both Poes,t and Pdi,t during inspiratory efforts, but not during relaxation. These studies confirm that twitch pressures induced by CMS during inspiratory efforts can be assessed at the mouth in normal subjects, providing a simple and non-invasive technique for assessing diaphragm activation during voluntary inspiratory efforts. Potentially, this technique could be made more sensitive and accurate and applied to detect submaximal efforts in patients.
Pulmonary haemodynamics in obstructive sleep apnoea: time course and associated factors
Authors: Schafer H , Hasper E , Ewig S , Koehler U , Latzelsberger J , Tasci S , Luderitz B
Published: November 2002

Changes in pulmonary artery pressure within an obstructive apnoea and elevations of transmural pulmonary artery pressure (Ppa,tm) towards the end of apnoea are well known. The purpose of our study was to examine which factors contribute to the increase of Ppa,tm in an apnoea. In addition, the time course of Ppa,tm and associated factors during a sleep study was investigated. We analysed the association of changes in arterial oxygen saturation (Sa,O2), oesophageal pressure (Poes) to estimate intrathoracic pressure, systolic blood pressure (BPsys) to estimate left ventricular afterload, apnoea duration and the change in Ppa,tm (deltaPpa,tm) during the course of obstructive apnoeas. Consecutive apnoeas in nonrapid eye movement (NREM)-sleep at the beginning, the middle and the end of the sleep study were analysed in six patients with obstructive sleep apnoea. The mean systolic Ppa,tm was 28.0+/-12.1 mmHg at the beginning of apnoea and 38.6+/-15.5 mmHg at the end (deltaPpa,tm 10.5+/-7.4 mmHg; p<0.0001). DeltaSa,O2 (p<0.0001; odds ratio (OR) 1.45; confidence interval (CI) 1.20-1.76) and deltaPoes (p<0.0001; OR 1.22; CI 1.11-1.34) were independently associated with deltaPpa,tm in a multiple regression analysis. Apnoea duration as well as deltaPoes, deltaPpa,tm and deltaSa,O2 were all significantly higher (p<0.05) in apnoeas at the middle of the sleep study than at the beginning or the end. In conclusion, hypoxaemia and mechanical factors as an increase in negative thoracic pressure contribute to elevations of the transmural pulmonary artery pressure during an obstructive apnoea. The time course of pulmonary haemodynamics within a steep study reveals that the highest transmural pulmonary artery pressure occurs in the middle of the night with no progressive increase towards the end of the sleep study.
A simple breathing circuit minimizing changes in alveolar ventilation during hyperpnoea
Authors: Sommer LZ , Iscoe S , Robicsek A , Kruger J , Silverman J , Rucker J , Dickstein J , Volgyesi GA , Fisher JA
Published: November 2002

Many clinical and research situations require maintenance of isocapnia, which occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple, passive circuit that minimizes changes in V'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea, the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO2) approximates that of mixed venous blood and therefore contributes minimally to V'A. Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5 and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4 mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit, Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six anaesthetized, intubated dogs were first ventilated at control levels and then hyperventilated by stepwise increases in either respiratory frequency (fR) from 10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg), p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea.
Sarcoidosis: immunopathogenetic concepts and their clinical application
Authors: Muller-Quernheim J
Published: November 2002

Our understanding of the immunopathogenesis of sarcoidosis has been advanced by studies of bronchoalveolar lavage cells. Activated macrophages and T-cells have been identified in different compartments of the sarcoid lung and the characteristics of the activation suggest that the cells become activated in the course of a normal immune response. The immune cells communicate via a cytokine network and the measuring of cytokine levels yields subgroups of sarcoidosis patients with different courses of the disease indicating different states of activation of the disease-mediating immune cells. The causative agent of sarcoidosis has not yet been identified; however, some of the described mechanisms can be clinically applied either to detect patients at risk of deterioration or to develop new therapeutic strategies. Using these approaches methotrexate, pentoxifylline and thalidomide have been identified as drugs which effectively suppress sarcoid inflammation and the serum level of soluble interleukin-2 receptors has been delineated to be a serum marker of sarcoid inflammation. Furthermore, analysing the pulmonary cytokine network in sarcoidosis will yield new staging parameters possibly supplying prognostic information and guiding therapeutic intervention.
A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency
Authors: O'Brien A , Blaivas M , Albers J , Wald J , Watts C
Published: November 2002

Mitochondrial myopathy is a rare cause of dyspnoea and respiratory failure, usually presenting in infancy. We describe a 27 yr old woman with a partial cytochrome c oxidase enzyme deficiency causing respiratory muscle weakness and respiratory failure. The onset was acute, with no preceding respiratory symptoms. The patient was successfully treated with bilevel positive airway pressure therapy.
Polypoid bronchial lesions due to Scedosporium apiospermum in a patient with Mycobacterium avium complex pulmonary disease
Authors: Murayama T , Amitani R , Tsuyuguchi K , Watanabe I , Kimoto T , Suzuki K , Tanaka E , Kamei K , Nishimura K
Published: November 2002

A 69 yr old female was hospitalized for further examination of abnormal shadows on chest radiographs. She had a history of tuberculous pleurisy, rheumatoid arthritis and gold-induced interstitial pneumonia. On admission she still suffered from rheumatoid arthritis. A chest computed tomography scan on admission showed clusters of small nodules in subpleural regions of both lungs combined with bronchiectasis. Mycobacterium avium complex was cultured repeatedly from the sputum. Bronchoscopic examination disclosed white-yellow polypoid lesions in the orifice of the left B4 bronchus. Cultures of the brushing specimen of the polypoid lesions and bronchial aspirates from the B4 bronchus yielded smoky-grey mycelial colonies that were later identified as Scedosporium apiospermum. It was concluded that the polypoid bronchial lesions due to Scedosporium apiospermum were formed in the preexisting dilated bronchus caused by Mycobacterium avium complex pulmonary disease.
Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP
Authors: Nagai S , Kitaichi M , Itoh H , Nishimura K , Izumi T , Colby TV
Published: November 2002

Based on past difficulties in clinically differentiating patients with idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans-organizing pneumonia (BOOP), and nonspecific interstitial pneumonia/fibrosis (NSIP), which all manifest clinically as interstitial lung disease, experience with pathologically confirmed examples of the three diseases was reviewed to compare clinical profiles and prognosis and to define NSIP more clearly. Thirty-one patients (15 males and 16 females) were pathologically identified as NSIP and subclassified into either the cellular (n=16) or fibrotic group (n=15). All 31 patients were clinically considered to be idiopathic NSIP cases. Patients with idiopathic BOOP (n=16) and IPF (n=64) were compared with the NSIP patients. Subacute presentation of interstitial lung disease characterized both idiopathic NSIP and idiopathic BOOP. NSIP patients showed volume loss on a chest radiograph (29.0%) and honeycombing on a computed tomography scan (25.8%); these features were not found in BOOP patients. Bronchoalveolar lavage lymphocytosis was characteristic of both BOOP and NSIP. Two subgroups of NSIP can be recognized histologically: patients in the fibrotic group had a less favourable outcome than those in the cellular group. BOOP and NSIP had a more favourable outcome than IPF. In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopathic interstitial pneumonia, both pathologically and clinically.
Bronchoscopy with transbronchial biopsies: measurement of bleeding volume and evaluation of the predictive value of coagulation tests
Authors: Bjortuft O , Brosstad F , Boe J
Published: November 2002

The objectives of this study were to measure the bleeding volume associated with fibreoptic bronchoscopy with transbronchial biopsies (TBB), to correlate it with coagulation tests and to compare bleeding volume in patients with and without lung transplant. A total of 104 consecutive TBB in 51 different patients was evaluated prospectively. Before each procedure, haemoglobin, blood platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT) and bleeding time were measured. During the procedure, lavage fluid and blood were collected by suction. The haemoglobin concentration of the mixture was measured and bleeding volume was calculated. Clinically significant bleeding was arbitrarily defined as >20 mL blood present in lavage fluid. The mean+/-SD bleeding volume was 7+/-10 mL with no statistically significant difference between transplanted and nontransplanted patients. In eight procedures (7.7%) the bleeding volume was >20 mL (range 22-61 mL). Prebiopsy values for blood platelet counts, PT and aPTT did not predict a bleeding tendency in any of the procedures in which significant bleeding occurred. No correlation was found between bleeding time and bleeding volume in the 17 procedures performed in patients with a prolonged bleeding time (> or =10 min). The bleeding associated with transbronchial biopsies was usually minor and quantitatively similar in patients with or without lung transplant. Coagulation tests could not predict clinically significant bleeding, which may occur in patients with normal coagulation test results.
Two-year results after lung volume reduction surgery in alpha1-antitrypsin deficiency versus smoker's emphysema
Authors: Cassina PC , Teschler H , Konietzko N , Theegarten D , Stamatis G
Published: November 2002

Lung volume reduction surgery (LVRS) improves exercise capacity and relieves dyspnoea in patients with smoker's emphysema (SE). It is unclear, however, whether LVRS similarly improves lung function in alpha1-antitrypsin-deficiency emphysema (alpha1 E). To address this question, this study prospectively compared the intermediate-term functional outcome in 12 consecutive patients with advanced alpha1E and 18 patients with SE who underwent bilateral LVRS. Before surgery there were no statistically significant differences between the two groups in the six-minute walking distance, dyspnoea score, respiratory mechanics or lung function data, except for the forced expiratory volume in one second, which was lower in the deficient group (24 versus 31% of the predicted value; p<0.05). In both groups, bilateral LRVS produced significant improvements in dyspnoea, the six-minute walking distance, lung function and respiratory mechanics. In the alpha1E group, the functional data, with the exception of the six-minute walking distance, returned to baseline at 6-12 months postoperation and showed further deterioration at 24 months. The functional status of the SE group remained significantly improved over this period. In conclusion, the functional improvements resulting from bilateral lung volume reduction surgery are sustained for at least 2 yrs in most patients with smoker's emphysema, but this type of surgery offers only short-term benefits for most patients with alpha1E.
Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema
Authors: Takeyabu K , Betsuyaku T , Nishimura M , Yoshioka A , Tanino M , Miyamoto K , Kawakami Y
Published: November 2002

This study examined the role of cysteine proteinases and their inhibitor in the development of emphysema in comparison with neutrophil elastase (NE) complexed with alpha1-protease inhibitor (NE-alpha1-PI), which was previously demonstrated to be increased in bronchoalveolar lavage (BAL) fluid from subjects with subclinical emphysema. Eight nonsmokers and 31 current smokers with (n=17) and without (n=14) emphysema, as evidenced by lung computed tomographic scans, were studied. The concentrations of immunologically detected cathepsin L and cystatin C, but not cathepsin B, were significantly increased in BAL fluid from the smokers with emphysema compared with those without emphysema, although the activity of cathepsin L, measured using a synthetic substrate and cathepsin L, released from cultured alveolar macrophages at 24 h, did not show any significant difference between the two groups. When comparison was made only for the subjects aged <60 yrs, the difference between the two groups disappeared for cathepsin L, but remained for NE-alpha1-PI. There was no significant correlation between the level of cathepsin L and that of NE-alpha1-PI in BAL fluid from the subjects with emphysema. In conclusion, increased levels of cathepsin L and cystatin C were demonstrated in bronchoalveolar lavage fluid from subjects with subclinical emphysema. However, the roles of cathepsin L and neutrophil elastase in the development of emphysema may vary between subjects and between the young and the old.
Bronchial obstruction and exhaled nitric oxide response during exercise in cold air
Authors: Therminarias A , Oddou MF , Favre-Juvin A , Flore P , Delaire M
Published: November 2002

This study examines whether exhausting exercise in cold air induces bronchial obstruction and changes in exhaled [NO] and in exhaled NO output (V'NO). Thus, eight well-trained males performed two incremental exercise tests until exhaustion, followed by 5 min of recovery in temperate (22 degrees C) and cold (-10 degrees C) environments, at random. At -10 degrees C, they were dressed in warm clothes. Ventilation (V'E), oxygen consumption (V'O2), carbon dioxide production, cardiac frequency (fC), and [NO] and V'NO were measured continuously. Before and after each test, the subjects' maximal expiratory flow-volume curves and peak expiratory flow, forced expiratory volume in one second (FEV1) and forced expiratory flow at 25 (FEF25), 50 (FEF50) and 75% (FEF75) of forced vital capacity were determined. At -10 degrees C, significant decreases in FEV1 and FEF75 were observed after exercise. At rest and at the same submaximal intensity, V'O2, V'E and fC did not differ significantly. At rest and up to approximately 50% peak V'O2, [NO] and V'NO values were lower at -10 degrees C than at 22 degrees C. Thereafter, and during recovery, the V'NO response became similar at both -10 and 22 degrees C. This study confirms that considerable hyperpnoea in cold air causes a detectable airway obstruction. This airway cooling also induces an initial decrease in the exhaled NO response. Since endogenous NO-production is involved in bronchial dilation, it cannot be excluded that this lack of production may favour the appearance of airway obstruction.
Hypocapnia-induced contraction of porcine airway smooth muscle
Authors: Lindeman KS , Croxton TL , Lande B , Hirshman CA
Published: November 2002

Hypocapnia constricts peripheral airways in vivo. This study investigated the role of airway smooth muscle in this phenomenon and the mechanism of hypocapnia-induced contraction in vitro. Isometric tension, intracellular pH (pHi) and intracellular free calcium concentration ([Ca2+]i) were measured in porcine airway smooth muscles suspended in organ baths in the presence of 5% or 0% CO2. In tracheal strips precontracted with carbachol, hypocapnic challenge (0% CO2) produced increases in tension, pHi, and [Ca2+]i. In bronchial rings or tracheal strips precontracted with carbachol, nifedipine administered between consecutive contractions attenuated responses to hypocapnia (75+/-11% above carbachol-precontracted tension before nifedipine versus 39+/-9% after nifedipine, n=7 bronchial rings, p<0.05). Neither indomethacin (5 microM), nordihydroguaiaretic acid (10 microM) nor phenidone (10 microM) significantly altered responses. These data suggest that enhanced Ca2+ influx through voltage-dependent Ca2+ channels of airway smooth muscle cells is important in airway responses to hypocapnia.
Concurrent measurement of smooth muscle shortening, lumen narrowing and flow to acetylcholine in large and small porcine bronchi
Authors: Mitchell HW , Cvetkovski R , Sparrow MP , Gray PR , McFawn PK
Published: November 2002

Models of airway function indicate that responsiveness (flow reduction) to bronchoconstrictor provocation depends on airway smooth muscle shortening and airway wall morphology. The contribution of these factors to the responsiveness of central and peripheral bronchi was assessed. Lumen flow was recorded in porcine perfused small (2 min i.d.) and large bronchial segments (6 mm i.d.). Lumen diameter was recorded in the same airways after inserting an endoscope. Smooth muscle shortening, relative wall area (WAr), smooth muscle and cartilage thickness and mucosal folds were measured morphometrically. The effect of acetylcholine (ACh; 10(-6)-10(-1) M) on functional measurements was determined by curve fitting. Maximum muscle shortening was 30% in small and 19% in large bronchi (p<0.01) and lumen narrowing was 49% and 39%, respectively. High doses of ACh stopped flow in small bronchi, but produced a plateau in large bronchi. Small airways were 250-times more sensitive to ACh than large airways, for all measurements. Smooth muscle and cartilage thickness and numbers of mucosal folds were greater in large than in small bronchi (p< or =0.01). Lumen narrowing and flow reduction were greater than predicted on the basis of muscle shortening and WAr (p<0.05). The structure of airways from the two groups was qualitatively similar, but responses were markedly different. Greater narrowing and flow responses of small bronchi were directly associated with smooth muscle responsiveness in situ. The results suggest that in vivo changes in airway wall shape or dimensions, or luminal secretions, exert a significant effect on airway flow, particularly in the small airways.
Rhinitis alone or rhinitis plus asthma: what makes the difference?
Authors: Magnan A , Fourre-Jullian C , Jullian H , Badier M , Lanteaume A , Vervloet D , Charpin D
Published: November 2002

This paper examines the clinical expression of asthma in a group of patients displaying rhinitis according to age, sex, associated symptoms, smoking, familial history of asthma, atopy, type of sensitization to aeroallergens (pollens and/or indoor allergens), total serum immunoglobulin E (IgE), and blood eosinophils. A total of 117 adults with rhinitis were analysed on the basis of symptoms. Among them, 51 also displayed asthma, defined as a history of recurrent episodes of dyspnoea with a reversible airflow obstruction or a positive methacholine challenge. The logistic regression analysis carried out in a stepwise approach, combining several factors, showed that various parameters affected the risk of having asthma associated with rhinitis. A further analysis was made in 74 rhinitis patients comparing 42 subjects without nonallergic airway hyperresponsiveness (NAAH) to 32 patients with asthma and NAAH. Atopy, high total serum IgE levels, elevated blood eosinophil count and maternal asthma were associated with asthma. Furthermore, in atopic patients, pollen sensitization was more closely related to rhinitis alone, whereas sensitization to indoor allergens was a major determinant for the association of asthma with the symptoms of rhinitis. The same risk factors as those found in the clinical part of the study discriminated the patients with rhinitis without NAAH from those with rhinitis, asthma and NAAH. In conclusion, this study gives new insights into the relationships between asthma and rhinitis.
An inhaled steroid improves markers of airway inflammation in patients with mild asthma
Authors: Jatakanon A , Lim S , Chung KF , Barnes PJ
Published: November 2002

Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma.
Perception of respiratory symptoms after methacholine-induced bronchoconstriction in a general population
Authors: Devereux G , Hendrick DJ , Stenton SC
Published: November 2002

In an epidemiological study, methacholine-induced bronchoconstriction was used as a physical illustration of the sensations associated with asthma. The objective of this study was to assess whether familiarity with these sensations could be used as a measure of asthma prevalence. Eight hundred and seventy six subjects aged 20-44 yrs completed a respiratory questionnaire and a measurement of airway responsiveness (the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20)). Subjects were asked about their perception of, familiarity with and description of the respiratory sensations experienced at the time of maximal bronchoconstriction. The questionnaire-derived lifetime prevalences of wheeze, chest tightness and undue breathlessness were 43, 35 and 22% respectively. Asthma medication was used by 8% and the lifetime prevalence of diagnosed asthma was 12%. Quantifiable levels of airway responsiveness were measured in 34%, and airway responsiveness in the range considered to be consistent with untreated active asthma was present in 21%. Bronchoconstriction was perceived by 59%. Perception of bronchoconstriction was associated with the magnitude of bronchoconstriction, younger age, female sex and questionnaire-reported symptoms. Of subjects able to perceive bronchoconstriction, 58% reported previous experience of (familiarity with) the associated respiratory sensations. Familiarity with the sensations of bronchoconstriction was associated with questionnaire-reported symptoms, diagnosed asthma and increasing levels of airway responsiveness. There was poor agreement between the respiratory symptoms reported by questionnaire before the methacholine test and the words used to describe respiratory sensations induced by the test. Familiarity with the sensations of methacholine-induced bronchoconstriction has all the appropriate associations of a measure of asthma prevalence and may be a useful adjunct to symptom questionnaires and airway responsiveness measurements in epidemiological studies. A sizeable number of subjects can be identified with intermediate levels of airway responsiveness, who are able to perceive bronchoconstriction and are familiar with the sensations associated with it, yet who are not recognized to suffer from asthma.
LFA-1 expression by blood eosinophils is increased in atopic asthmatic children and is involved in eosinophil locomotion
Authors: Lantero S , Alessandri G , Spallarossa D , Scarso L , Rossi GA
Published: November 2002

Allergic asthma is characterized by eosinophil migration in the airways, which is strictly dependent on the expression of adhesion molecules. This study investigated whether the expression of adhesion molecules on eosinophils is increased and associated with disease activity in allergic asthma. Twenty atopic asthmatic (AA) subjects and nine controls were studied and the expression of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), Mac-1 (CD11b/CD18) and very late antigen-4 (VLA-4; CD49d/CD29) on blood eosinophils was evaluated by specific monoclonal antibody (Mab) staining and flow-cytometric analysis. Compared with controls, eosinophils from AA showed increased expression of LFA-1 (p<0.005), but not of Mac-1 or VLA-4 (p>0.1). In addition, LFA-1 expression correlated positively with blood eosinophil number (r=0.792, p<0.05), while no correlations were observed between Mac-1 or VLA-4 expression and blood eosinophil number. The migration of eosinophils through human umbilical vein endothelial cells with or without anti-LFA-1, Mac-1 and VLA-4-blocking Mab was studied. Compared with controls, eosinophils from AA showed increased migration toward C5a (p<0.01). Cell migration was totally inhibited by preincubating eosinophils with anti-LFA-1 (p<0.05), while anti-Mac-1 had no effect (p>0.1). Thus, the expression of lymphocyte function-associated antigen-1 by blood eosinophils is increased in atopic asthmatics and seems to modulate the enhanced eosinophil migration observed in allergic asthma.
Urban-rural differences in questionnaire-derived markers of asthma in Kenyan school children
Authors: Odhiambo JA , Ng'ang'a LW , Mungai MW , Gicheha CM , Nyamwaya JK , Karimi F , Macklem PT , Becklake MR
Published: November 2002

Grade 4 Kenyan children attending 10 randomly selected public primary schools in Nairobi (urban) and the Muranga District (rural) were surveyed to establish the prevalence of symptom markers of asthma and to assess the impact of urbanization. A respiratory health and home environment questionnaire was administered at school to parents or guardians. The questionnaire response rates were 94.2% (568/ 603) for Nairobi and 89.6% (604/674) for Muranga. The prevalence rates for asthma, defined as "attacks of shortness of breath with wheeze", were 95% for urban and 3.0% for rural children (odds ratio (OR) urban versus rural: 3.42; 95% confidence interval (CI): -1.96-5.91). This urban-rural gradient persisted after adjusting for urban-rural differences in host factors (including duration of breastfeeding and family history of asthma and/or allergy), but was largely explained by urban-rural differences in environmental factors, including indoor animals, sharing a bedroom with a smoker, parental education, house ventilation and exposure to motor vehicle fumes en route to school (adjusted OR: 1.59; 95% CI: 0.70-3.55). Similar results were obtained for all other symptoms. These findings confirm the clinical impression that asthma is an important illness in Kenya and underline the need for the further study of environmental factors amenable to intervention, particularly in urban areas.
Analysis of expiratory tidal flow patterns as a diagnostic tool in airflow obstruction
Authors: Morris MJ , Madgwick RG , Collyer I , Denby F , Lane DJ
Published: November 2002

An index obtained from tidal expiration, the ratio of time to peak tidal expiratory flow (tPTEF) to expiratory time (tE), discriminates between groups with and without airflow obstruction in infants and children and correlates with other measurements of airflow obstruction in adults. The aim of this study was to determine whether the diagnosis of airflow obstruction could be made from an analysis of the later part of the expiratory tidal flow time curve, i.e beyond the maximum flow. One hundred and eighteen patients attending the lung function laboratory with a putative diagnosis of airflow obstruction were studied. From uncoached tidal breathing, measurements were made of the average time constant of the respiratory system (Trs) and extrapolated volume (EV). Forced expiratory spirometry and whole-body plethysmography were performed. In this cross-sectional study, Trs correlated with inspiratory airways resistance and forced expiratory volume in one second (FEV1), according to the linear regression equations, airway resistance (Raw)=3.03 Trs+1.2, r=0.65, p<0.001, and FEV1% predicted = 87.8-23.7 Trs, r=058, p<0.001. EV correlated positively with overinflation, functional residual capacity (FRC) % pred = 152 EV+103, r=0.68, p<0.001. This study shows that there is a relationship between these measurements made from analysis of tidal breathing and recognized measurements of airflow obstruction and overinflation.
Tidal expired airflow patterns in adults with airway obstruction
Authors: Williams EM , Madgwick RG , Morris MJ
Published: November 2002

Earlier studies have shown that time and flow indices derived from tidal expiratory flow patterns can be used to distinguish the severity of airway obstruction. This study was designed to address two aspects of tidal expiratory flow patterns: 1) how do expiratory flow patterns differ between subjects with normal and obstructed airways; and 2) can a sensitive index of airway obstruction be derived from these pattern differences? Tidal expiratory flow patterns from 66 adult subjects with varying degrees of airway obstructive disease with a forced expiratory volume in one second (FEV1) of 20-121% predicted were examined. In each subject, the expired flow pattern from each consecutive breath was scaled and then averaged together to create a single expired pattern. A detailed examination of the scaled flow patterns in 12 subjects (six with normal airways and six with airway obstruction) showed that the shape of the post-peak expiratory flow portion was different in the subjects with airway obstruction. A slope index, S, was derived from the scaled patterns and found to be sensitive to the severity of airway obstruction, correlating with FEV1 (% pred) with r2=0.74 (p<0.05, n=57). The S index also correlated (r2=0.36, p<0.05, n=47) with the functional residual capacity (FRC) (% pred) which was >100% in subjects with severe airway obstruction and lung overinflation. In subjects with normal airways, three further airflow patterns could be distinguished, which were different from the patterns seen in subjects with the severest airway obstruction. Scaled flow patterns from tidal expiration collected from uncoached subjects, can be used to derive an index of airway obstruction.
Pulmonary function in sickle cell disease with or without acute chest syndrome
Authors: Santoli F , Zerah F , Vasile N , Bachir D , Galacteros F , Atlan G
Published: November 2002

Recurrent acute chest syndrome (ACS) has been suggested as a risk factor for chronic lung dysfunction in sickle cell disease. To investigate this hypothesis, lung function tests were performed in 49 sickle cell disease outpatients whose condition was stable, including 23 patients with a history of two to four episodes of ACS (ACS+) and 26 with no history of ACS (ACS-). The two groups were comparable regarding the sex ratio, body mass index, smoking history, physical characteristics, clinical history and usual lung function tests. Respiratory resistance (Rrs), measured using the forced oscillation technique, increased with the number of ACS episodes (r=0.55, p<0.0001) and a significant relationship was observed between Rrs as an independent variable and the expiratory flow rates at 25, 50 and 25-75% of the forced vital capacity as explanatory variables (r= 0.36, p<0.02; r=0.35, p<0.02; and r=0.4, p<0.006, respectively), with higher Rrs being associated with lower expiratory flow rates. The transfer factor (TL,CO) and transfer coefficient (KCO) for CO were significantly higher in the ACS+ group than in the ACS-group (TL,CO=84+/-4 versus 71+/-3%, p<0.004 and KCO=102+/-5 versus 90+/-3%, p<0.05, respectively). The data demonstrate that obstructive lung dysfunction is fairly common in sickle cell disease and suggest that recurrent acute chest syndrome may contribute specific obstructive defects. The increase in respiratory resistance associated with acute chest syndrome was accompanied by an increase in diffusion capacity, suggesting that it may have been related to an increase in lung blood volume.
Lung function and exercise capacity in thalassaemia major
Authors: Cracowski C , Wuyam B , Klein V , Levy P
Published: November 2002

Lung function abnormalities in thalassaemia major are various and complex; however, patients still die from cardiac lesions. This study aimed to investigate pulmonary and cardiac involvement at an early stage in thalassaemic patients and study their respective implications at rest and during exercise. Ten patients (five adults and five children) with thalassaemia major were investigated by echocardiography, lung function and exercise testing a few days after transfusion. All have had regular transfusions and chelation with deferoxamine and none had chronic pulmonary disease symptoms. Minor lung function abnormalities were found: two patients had moderate obstructive syndrome and two had a decreased carbon monoxide transfer factor. Hypoxaemia was never found at rest and no desaturation was observed at the end of exercise. Echocardiographic abnormalities were also moderate. Peak oxygen consumption (V'O2) was decreased in three adults and was lower in adults than children (means 27.7+/-4.6 and 41.1+/-4.8 mL.kg(-1).min(-2) respectively). The V'O2/cardiac frequency slope was lower in adults than children (0.25+/-0.06 versus 0.42+/-0.10 mL.kg(-1).min(-2)), whereas end-exercise breathing reserve was >40% maximal voluntary ventilation for all patients. In conclusion, none of the patients had ventilatory limitations but older patients had cardiac limitations assessed by the relationship between oxygen consumption and cardiac frequency. Exercise testing may detect cardiac impairment in thalassaemia major earlier than investigations at rest.
Immunolocalization of G(alpha)i-3 in foetal lung fibroblasts
Authors: Dosanjh A
Published: November 2002

Guanosine triphosphate (GTP)-binding proteins or G proteins are involved in a wide variety of well-recognized signalling activities between cell surface receptors and effectors. The heterotrimeric G proteins have alpha,beta and gamma subunits organized in a trimeric structure. The aim of this study was to localize G(alpha)i-3, an important heterotrimeric G protein, in foetal lung cells. Using a foetal lung fibroblast cell line (RFL-6), the localization of G(alpha)i-3 was determined by immunofluorescence using a specific antibody to G(alpha)i-3, colocalization with a lectin known to bind the Golgi complex and Western blotting of RFL-6 cellular membrane proteins. This study identified G(alpha)i-3 on the Golgi membranes in rat foetal lung cells. Treatment with cycloheximide, to block protein synthesis, diminished the cytosolic distribution of the protein, but intense Golgi staining remained. G(alpha)i-3, therefore, appears to be part of the Golgi complex and not present transiently during protein synthesis. In the nonpolar foetal lung fibroblasts studied, the intracellular concentration of G(alpha)i-3 suggests a role for this protein in the intracellular trafficking and regulation of proteins needed for normal lung development.
A 50-kDa variant form of human surfactant protein D
Authors: Mason RJ , Nielsen LD , Kuroki Y , Matsuura E , Freed JH , Shannon JM
Published: November 2002

The dominant form of human surfactant protein D (SP-D) is a multimeric collagenous glycoprotein composed of monomeric subunits that have a molecular mass of 43 kDa under reducing conditions. However, in evaluating monoclonal antibodies to human SP-D, an additional monomeric subunit was identified with a reduced molecular mass of 50 kDa. This 50-kDa variant was detected in approximately half of the samples evaluated and was found in lavage fluid from normal subjects, patients with alveolar proteinosis or idiopathic pulmonary fibrosis and in amniotic fluid. This 50-kDa variant had the same amino-terminal sequence, amino acid composition and apparent size of the carboxy-terminal collagenase-resistant fragment (20 kDa) as the 43-kDa subunit. The major difference was in the amino-terminal portion of the molecule and was due to altered glycosylation, as determined by carbohydrate staining, chemical deglycosylation, treatment with N-glycanase and neuraminidase and reduced signals for threonine at positions 5, 9 and 10 during amino-terminal sequencing. After gel filtration chromatography, the 50-kDa form was not present in the high molecular weight fraction, which is commonly used in purification of SP-D, but was found only in the smaller molecular weight fraction of monomers and trimers of SP-D. In conclusion, the 50 kDa-form of surfactant protein D is produced by post-translational glycosylation and does not form higher ordered oligomers, but its precise physiological function remains to be determined.
Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome
Authors: Sampol G , Munoz X , Sagales MT , Marti S , Roca A , Dolors de la Calzada M , Lloberes P , Morell F
Published: November 2002

Weight loss is associated with clinical improvement in sleep apnoea/ hypopnoea syndrome (SAHS). The aim of this study was to ascertain whether the therapeutic efficacy of dietary weight loss is maintained in the long-term. From a total of 216 overweight SAHS patients treated by only a weight reduction programme, 24 cured by this method (apnoea/hypopnoea index (AHI) at diagnosis 443+/-27.8, after weight loss 3+/-3.1) were re-evaluated after a mean (+/-SD) period of 94.3+/-27.4 months post-cure. No correlation was found between changes in AHI and body mass index experienced by each patient in the two phases of the study (diagnosis to cure and cure to long-term follow-up), r=0.29, p=0.156, demonstrating a marked intra-individual variability. Six of the 13 patients who maintained their weight presented recurrence of SAHS (AHI 40.5+/-24.1) as did eight of the 11 who had regained weight (AHI 44.3+/-23.). Weight maintenance was more frequent among patients who had continued to attend periodic appointments, 10/11 versus 3/13 (p<0.001). In conclusion, weight-loss efficacy is maintained in the long-term in some sleep apnoea/hypopnoea syndrome patients. This study indicates the need for periodic follow-up of these patients as a reinforcement for weight maintenance and for early detection of the reappearance of sleep apnoea/hypopnoea syndrome.
Acute effects of inhaled nitric oxide in adult respiratory distress syndrome
Authors: Iotti GA , Olivei MC , Palo A , Galbusera C , Veronesi R , Braschi A
Published: November 2002

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.