bluuebunny/crossref_metadata_2025 huggingface dataset:
Breathing pattern during acute respiratory failure and recovery
Authors: Del Rosario N , Sassoon CS , Chetty KG , Gruer SE , Mahutte CK
Published: January 2003

The objective of this study was to compare the breathing pattern of patients who failed to wean from mechanical ventilation to the pattern during acute respiratory failure. We hypothesized that a similar breathing pattern occurs under both conditions. Breathing pattern, mouth occlusion pressure (P[0.1]) and maximum inspiratory pressure (P[I,max]) were measured in 15 patients during acute respiratory failure, within 24 h of the institution of mechanical ventilation, and in 49 patients during recovery, when they were ready for discontinuation from mechanical ventilation. The following indices were calculated: rapid shallow breathing index (respiratory frequency/tidal volume (fR/VT)); rapid shallow breathing-occlusion pressure index (ROP = P[0.1 x fR/VT]); P(0.1)/P(I,max); and effective inspiratory impedance (P[0.1]/VT/(inspiratory time (tI)). Patients who failed to wean (n=11) had a similar ROP,fR/VT and P(0.1)/P(I,max) to those with acute respiratory failure despite a significantly reduced P(0.1)/VT/tI, the value of which was comparable to that of patients who weaned successfully (n=38). The P(I,max) of patients who failed to wean was similar to that of patients who weaned successfully. We conclude that patients who failed to wean had a breathing pattern similar to that during acute respiratory failure, despite a reduced mechanical load on the respiratory muscles and a relatively adequate inspiratory muscle strength. This suggests that strategies that enhance respiratory muscle endurance may facilitate weaning.
Site of upper airway obstruction in obstructive apnoea and influence of sleep stage
Authors: Boudewyns AN , Van de Heyning PH , De Backer WA
Published: January 2003

Various sites along the upper airway (UA) are prone to narrow and collapse in patients affected by obstructive sleep apnoea. Sleep stages may eventually alter these sites. The present study was designed to determine the site(s) of UA obstruction and the influence of sleep stage on the pattern of obstruction. Twenty eight obstructive sleep apnoea patients underwent UA pressure measurements during polysomnography. Solid-state pressure sensors were located at the nasopharynx, oropharynx, tongue base, hypopharynx and oesophagus and the lower limit of UA obstruction was determined relying on the observed pressure pattern. The site of UA obstruction varied among consecutive apnoeas in all but two patients. The lower limit of UA obstruction was predominantly located at the nasoand oropharynx. Rapid eye movement (REM) sleep was associated with a tendency for obstruction to extend towards lower levels of the UA and nasopharyngeal occlusion was significantly less observed during REM compared to oropharyngeal obstruction. Upper airway obstruction involves more than one specific site of the upper airway in the majority of sleep apnoea patients. Obstruction at lower levels of the upper airway is more likely to be observed during rapid eye movement sleep.
Effect of zopiclone on sleep, night-time ventilation, and daytime vigilance in upper airway resistance syndrome
Authors: Lofaso F , Goldenberg F , Thebault C , Janus C , Harf A
Published: January 2003

We have assessed the effects of zopiclone (7.5 mg), a new cyclopyrrolone hypnotic drug, on ventilation, sleep parameters, and daytime vigilance in snorers with upper airway resistance syndrome (UARS). Using a randomized double-blind design, eight male patients with UARS took either oral zopiclone or a placebo each evening for seven consecutive days and then crossed over to the other drug after a 7 day placebo period. Polysomnography followed by a multiple sleep latency test (MSLT) was performed during the last night of each treatment period. Zopiclone produced significant improvements in the sleep efficiency index (total sleep time/time in bed) (placebo 84+/-15% versus zopiclone 91+/-7%) and average MSLT (placebo 10.3+/-3.7 min versus zopiclone 14.9+/-2.8 min), as well as nonsignificant improvements in sleep onset latency and total sleep time. It had no effect on sleep architecture or on the arousal index (placebo 17+/-8 arousals x h(-1) versus zopiclone 17+/-4 arousals x h[-1]). Furthermore, none of the respiratory parameters were significantly affected by zopiclone. In conclusion, zopiclone has no adverse effects on sleep architecture, respiratory parameters during sleep, and daytime sleepiness in patients with UARS.
Five-year effects of nasal continuous positive airway pressure in obstructive sleep apnoea syndrome
Authors: Chaouat A , Weitzenblum E , Kessler R , Oswald M , Sforza E , Liegeon MN , Krieger J
Published: January 2003

There have been very few studies assessing the long-term physiological effects of nasal continuous positive airway pressure (CPAP) for the obstructive sleep apnoea syndrome. We therefore investigated prospectively the evolution of lung function, arterial blood gases and pulmonary haemodynamics in patients with this syndrome treated with CPAP. Sixty five patients were included. The mean duration of home treatment with nasal CPAP was 64+/-6 months. Most of the patients (77%) were smokers at the baseline assessment. We observed a small, but significant, decrease in forced expiratory volume in one second (FEV1) from 80+/-21% at baseline (t0) to 76+/-21% of the predicted value at the follow-up evaluation (t5) (p<0.01). Arterial oxygen tension (P[a,O2]) for the group as a whole remained stable (9.4+/-1.5 kPa (71+/-11 mmHg) versus 9.4+/-1.2 kPa (71+/-9 mmHg)). However, P(a,O2) increased in the subgroup of patients with hypoxaemia at t0 (n=23), from 7.8+/-0.7 kPa (59+/-5 mmHg) to 8.9+/-1.2 kPa (67+/-9 mmHg). Arterial carbon dioxide tension (P[a,CO2]) for the group as a whole increased slightly, but significantly, from 5.2+/-0.7 kPa (39+/-5 mmHg) to 5.4+/-0.5 kPa (41+/-4 mmHg) (p<0.05). Mean pulmonary artery pressure (Ppa) at rest did not change (16+/-5 mmHg versus 17+/-5 mmHg; NS) nor did exercising Ppa. In the 11 patients with pulmonary hypertension at t0, Ppa was 24+/-5 mmHg at t0 versus 20+/-7 mmHg at t5 (NS). We conclude that the significant decrease of forced expiratory volume in one second after 5 yr follow-up was related to a high percentage of smokers and exsmokers in the study population. Daytime arterial oxygen tension and pulmonary artery pressure remained stable in an unselected series of 65 obstructive sleep apnoea syndrome patients treated for 5 yrs with nasal continuous positive airway pressure, unlike arterial carbon dioxide tension, which increased by a small, but significant, amount.
Oxygen cost of breathing and weaning process in newborn infants
Authors: Roze JC , Liet JM , Gournay V , Debillon T , Gaultier C
Published: January 2003

Newborn infants may have a high oxygen cost of breathing (OCB) at the time of being weaned from mechanical ventilation. We hypothesized that this increase in oxygen consumption (V'O2) could be reduced by using certain weaning ventilatory modes. We designed a study to assess V'O2 during three weaning ventilatory modes: patient triggered ventilation, synchronous intermittent mandatory ventilation (SIMV) and continuous positive airway pressure in 16 newborn infants before being weaned from mechanical ventilation In seven infants whose OCB was high. V'O2 was not significantly different between CV and PTV (8.9+/-0.6 versus 9.5+/-0.8, respectively) whereas it tended to increase to 10.8+/-1.1 mL x min(-1) x kg(-1) during SIMV and increased significantly to 11.9+/-0.8 mL x min(-1) x kg(-1). In the other nine infants whose OCB was normal, no significant variation of V'O2 was observed. Patient triggered ventilation was a weaning ventilatory mode that significantly reduced the increase in oxygen consumption observed in infants with a high oxygen cost of breathing, as compared to synchronous intermittent mandatory ventilation or continuous positive airway pressure. Further investigations in newborn infants with a high oxygen cost of breathing should be performed prior to routine use of patient triggered ventilation.
The simultaneous comparison of acetylene or carbon dioxide flux as a measure of effective pulmonary blood flow in children
Authors: Rosenthal M , Bush A
Published: January 2003

Both acetylene (Ac) and carbon dioxide can be used to measure effective pulmonary blood flow (Q'eff) noninvasively. They are safe and reasonably accurate in adults during rest and exercise, but there have been no simultaneous comparisons in children. One hundred and six healthy children (55 males and 51 females, aged 8-17 yrs) were studied using an Innovision quadrupole mass spectrometer. They all underwent five rebreathing manoeuvres at rest, and then single measurements were again taken after 9 min of bicycle exercise. Mixed venous CO2 levels were calculated either by a linear (L) or curvilinear (C) extrapolation method. At rest, the coefficients of variation for Q'eff were Ac 8%, L 20%, and C 16% (p<0.001). The median resting values were: Ac 3.2 (95% confidence interval (95% CI) 3.1-3.4) L 5.1 (95 % CI 4.6-5.4) and C 4.7 (95 % CI 4.3-5.1) L x min(-1) x m(-2), (p<0.001). Compared to Ac, only 14 and 17% of L and C values, respectively, were +/-0.5 L x min(-1) x m(-2), whilst 41 and 29%, respectively were more than +/-2 L x min(-1) x m(-2). During exercise, median values were: Ac 6.7 (95% CI 6.3-7.0); L 8.0 (95% CI 7.3-8.4); and C 7.2 (95% CI 6.5-7.9) L x min(-1) x m(-2). L was significantly greater than C (p<0.001), but C was similar to Ac (p=0.06). More than 50% of L and C values could not be calculated for various reasons, whereas all 106 Ac values could be calculated. Neither carbon dioxide method is sufficiently reliable to be used in children in a clinical setting. Acetylene was safe, reliable, accurate and preferred.
Cells and mediators from pharyngeal secretions in infants with acute wheezing episodes
Authors: Counil FP , Lebel B , Segondy M , Peterson C , Voisin M , Bousquet J , Arnoux B
Published: January 2003

An acute wheezing episode is the most common feature of severe lower respiratory tract infection during infancy. Respiratory syncytial virus (RSV) is the major causative agent. In order to study inflammation during acute wheezing episodes in infants, we wanted to assess the feasibility and contribution of induction of pharyngeal secretions. We therefore compared inflammatory markers in the pharyngeal secretions of 27 infants suffering from acute wheezing episodes with an RSV infection (RSV+) and 18 infants suffering with acute wheezing episodes without RSV infection (RSV-). Pharyngeal secretions were recovered by physiotherapy using isotonic saline. The safety of the procedure was carefully checked. Pharyngeal secretions were homogenized with dithiothreitol. Total cells and eosinophils were counted and levels of eosinophil cationic protein (ECP) and histamine were measured. Induction of pharyngeal secretion was always well tolerated. Eosinophils were present in five RSV+ and seven RSV- patients. ECP levels were not significantly different between the groups. Histamine levels after protein adjustment were significantly increased in RSV+ patients (p<0.01) in comparison to RSV- patients. In this study, we have shown, that pharyngeal secretion can be safely recovered from infants suffering from acute wheezing episodes, and that it can be analysed for enumeration of inflammatory cells and measurement of inflammatory mediators.
One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide
Authors: Nikolaizik WH , Preece MA , Warner JO
Published: January 2003

Inhaled corticosteroids have become a mainstay in the management of chronic asthma. Their use had been considered safe, although some degree of adrenal suppression has been demonstrated after 2 and 4 weeks of treatment with either 400 microg x day(-1) of beclomethasone dipropionate or budesonide. To weigh the benefits and risks of long-term treatment, 12 children with moderately severe asthma were assessed in a follow-up study on budesonide 200 microg b.i.d. After 1 yr, the nocturnal cortisol production was significantly reduced by 19%, but no greater compared to 2 and 4 weeks of treatment. Growth and growth hormone levels were normal. Lung function tests were significantly better, not only versus baseline values but also versus 2 and 4 weeks of treatment. We conclude that systemic effects of inhaled corticosteroids in conventionally low doses do not accumulate with length of treatment, whilst lung function parameters will continue to improve. Therefore, inhaled corticosteroids once started in asthmatic children not controlled on other medications should be continued, but their use should be carefully considered and the minimal dose required to control the asthma employed.
Repeatability of measures of inflammatory cell number in bronchial biopsies in atopic asthma
Authors: Sont JK , Willems LN , Evertse CE , Hooijer R , Sterk PJ , van Krieken JH
Published: January 2003

Airway pathology is increasingly considered to be a major outcome in asthma research. The aim of this study was to examine the intra-observer, within-section and between-biopsy repeatability, together with the implications for statistical power of a computerized quantitative analysis of inflammatory cell numbers in the lamina propria in bronchial biopsy specimens from atopic asthmatic subjects. Thirty six atopic adults (aged 19-40 yrs) with mild to moderate asthma (baseline forced expiratory volume in one second (FEV1) > or =50% of predicted value, methacholine (PC20) range 0.02-18.2 mg x mL[-1]) at various levels of treatment (25 subjects on inhaled steroids) entered the study. Biopsies were taken from the (sub)segmental carinae of the right lower and middle lobe and from the main carina. Specimens were snap-frozen and immunohistochemical staining was performed on cryostat sections with monoclonal antibodies against: (secreted) eosinophil cationic protein (EG1, EG2), mast cell tryptase (AA1), CD45, CD22, CD4, CD8, CD25, and CD45RO. Using a computerized system, the number of positively stained cells in the lamina propria was counted. When considering all cell types together, satisfactory intraclass correlation coefficients (ICC) values were obtained for intra-observer, within-section and between-biopsy repeatability, being 0.90, 0.80 and 0.81, respectively. The analysis of repeatability for individual cell types revealed ICC values ranging 0.47-0.82 for intra-observer, 0.44-0.76 for within-section and 0.37-0.67 for between-biopsy repeatability. The results imply that a sample-size between eight and 25 subjects is needed to detect at least one doubling difference in cell number per 0.1 mm2 for a particular inflammatory cell type in a study, using a within-group design with alpha=0.05 and power of 0.80. A sample-size of 13-48 subjects per group is required to detect the same difference between the groups in a parallel design.
Failure to detect the presence of Chlamydia pneumoniae in sarcoid pathology specimens
Authors: Blasi F , Rizzato G , Gambacorta M , Cosentini R , Raccanelli R , Tarsia P , Arosio C , Savini E , Cantoni C , Fagetti L , Allegra L
Published: January 2003

The pathogenesis of sarcoidosis is not yet known. On the basis of seroepidemiological data, an association between Chlamydia pneumoniae infection and sarcoidosis has been suggested, but so far no study has addressed the direct detection of this agent in the affected tissues. The aim of the present study was to detect C. pneumoniae deoxyribonucleic acid (DNA) within sarcoid tissue specimens by means of a two-step polymerase chain reaction. Lung biopsy specimens of 33 patients with histologically confirmed pulmonary sarcoidosis and 21 control lung biopsies or pathology specimens of patients with pulmonary carcinoma or emphysema were retrospectively analysed. A nested polymerase chain reaction was applied using two sets of primers designed to detect a fragment of the 16 strand ribosomal ribonucleic acid (rRNA) gene of C. pneumoniae. The results of the study failed to demonstrate the presence of C. pneumoniae in biopsy specimens of sarcoid tissue and in the control lung biopsies or pathology specimens. Our results, therefore, tend to rule out the possibility of a direct involvement of Chlamydia pneumoniae in the pathogenesis of sarcoidosis.
Inhalation challenges with agents causing occupational asthma
Authors: Vandenplas O , Malo JL
Published: January 2003

Occupational asthma (OA) is steadily emerging as the principal cause of respiratory disease due to the workplace environment. One of the key means to ascertain diagnosis of OA is specific inhalation challenge (SIC) with occupational agents. This review: 1) describes the methodology of SIC, with a special emphasis on procedures aimed at increasing the safety and validity of these tests; and 2) outlines the roles of SIC in the diagnosis of OA in clinical and medicolegal assessment, epidemiological studies, surveillance programmes and the investigation of the pathophysiological mechanisms of asthma and OA. We discuss areas of future development, including the development of apparatus which allows exposure of subjects to low and stable concentrations of the occupational agent and the assessment of preventive procedures.
New immunosuppressive regimens in lung transplantation
Authors: Briffa N , Morris RE
Published: January 2003

Survival after lung transplantation is less than 50% after 5 yrs and is limited by infection and obliterative bronchiolitis. There is, therefore, a need for new immunosuppressive regimens if we are to attempt to improve long-term survival. Several trials in lung transplantation of new immunosuppressive agents are in the planning stages. In this article, we review the experience with a new monoclonal agent (interleukin 2 (IL2) receptor antagonist) in kidney transplantation, together with the pharmacokinetic (PK) and pharmacodynamic properties and experience in transplantation in general, of the more promising of the new xenobiotic compounds (cyclosporine microemulsion, mycophenolate mofetil, tacrolimus and sirolimus). Recent novel approaches to the vexing problem of resistant lung rejection and obliterative bronchiolitis, such as the use of aerosolized cyclosporine, methotrexate, total lymphoid irradiation and phototherapy, are discussed. Finally an immunosuppressive regimen, using these new drugs in lung transplantation is suggested.
Pleural disease and acquired immune deficiency syndrome
Authors: Light RW , Hamm H
Published: January 2003

Patients with acquired immune deficiency syndrome (AIDS) do not frequently have pleural complications. However, pneumothorax is a troublesome complication of patients with AIDS. At some medical centres, more than 50% of patients with spontaneous pneumothorax have AIDS. Most patients with spontaneous pneumothorax and AIDS have Pneumocystis carinii infection and necrotic subpleural blebs. The pneumothoraces in these patients usually cannot be managed with tube thoracostomy alone. Patients who do not respond to tube thoracostomy are best managed with a Heimlich valve or with thoracostomy with stapling of blebs and pleural abrasion. Approximately 2% of human immunodeficiency virus (HIV)-positive individuals will have a pleural effusion. Parapneumonic effusions or empyema, tuberculosis and Kaposi's sarcoma are the three leading causes. P. carinii infection is frequently responsible for pulmonary infections, but is only occasionally responsible for a pleural effusion. Pleural effusions may also develop from non-Hodgkin's lymphoma (NHL). There is one relatively rare NHL that is associated with the Kaposi's sarcoma associated virus that produces a lymphoma confined to the body cavity.
Airway goblet cell mucin: its structure and regulation of secretion
Authors: Kim KC , McCracken K , Lee BC , Shin CY , Jo MJ , Lee CJ , Ko KH
Published: January 2003

Mucociliary clearance is a major function of the airway epithelium. This important function depends both on the physicochemical properties of the airway mucus and on the activity of the cilia. The former, in turn, is dependent mainly on the quality and quantity of mucous glycoproteins or mucins, which are produced by two different cell types, namely, goblet cells of the epithelium and mucous cells of the submucosal gland. Neither the structural nor the functional differences of mucins produced by these two cell types are yet known. The availability of primary airway epithelial cell culture systems, however, has made it possible to study the structure and regulation of airway goblet cells to some extent. The epithelial mucins are extremely hydrophobic and are associated with various macromolecules, the quality and quantity of which may also affect the physicochemical properties of the mucus. Secretion of epithelial mucins is stimulated by various factors, including a number of inflammatory agents. The recent progress in mucin molecular biological research will allow us to identify different mucin core proteins produced by those different cell types, and, hopefully, the differential functions of these mucins in health and disease.
Lung volume reduction surgery as an emergency and life-saving procedure
Authors: Hansson B , Jorens PG , van Schil P , van Kerckhoven W , van den Brande F , Eyskens E
Published: January 2003

Lung volume reduction surgery (LVRS) is emerging as a promising and unique therapeutic option for rigorously selected patients with severe debilitating emphysema. A 51 yr old man with generalized emphysema developed bilateral pneumothoraces during his first holiday abroad. Due to respiratory insufficiency, intubation and mechanical ventilation were necessary. In total, six chest tubes were inserted but massive air leak persisted and his respiratory condition deteriorated due to bronchopneumonia and sepsis. The patient was transferred to Belgium. As a last resort, bilateral LVRS was performed through a median sternotomy. The most diseased areas of the upper lobes containing the air leak were resected bilaterally and a pleurectomy was associated. Three months after operation, there was a remarkable improvement in spirometric values with an increase in forced expiratory volume in one second of almost 100%. The results were sustained after a follow-up of 18 months. In this dramatic case, lung volume reduction surgery proved to be effective, and was even a life saving procedure.
Clear cell sarcoma: an extremely rare cause of pleural disease
Authors: Bury T , Hermans G , Alexis-Agnant R , Chevalier P , Limet R , Bartsch P
Published: January 2003

We present the case of a 36 yr old woman with a persisting complaints of left chest pain. A chest radiograph revealed multiple left pleural thickenings. Classical exploration was negative. Thoracic surgery allowed the subtotal removal of a huge pleural tumour. The histological examination revealed a clear cell sarcoma. The literature on this extremely rare tumour is reviewed.
Nasal ventilation in pregnancy: treatment of nocturnal hypoventilation in a patient with kyphoscoliosis
Authors: Restrick LJ , Clapp BR , Mikelsons C , Wedzicha JA
Published: January 2003

The management of a young woman with congenital kyphoscoliosis, who developed symptomatic nocturnal hypoventilation during the third trimester of pregnancy, is described. Nasal intermittent positive pressure ventilation (NIPPV) was safely and effectively used to correct nocturnal hypoxaemia and hypercapnia from the 30th-36th week of gestation, when a healthy boy was delivered by Caesarean section. Following delivery, the mother no longer required NIPPV and returned to her prepregnancy level of activity.
Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension
Authors: Sitbon O , Humbert M , Jagot JL , Taravella O , Fartoukh M , Parent F , Herve P , Simonneau G
Published: January 2003

In a subset of patients with primary pulmonary hypertension (PPH), high doses of oral calcium-channel blockers (CCB) produce a sustained clinical and haemodynamic improvement. However, significant side-effects have been reported during acute testing with CCB. Therefore, to identify accurately patients who may benefit from long-term CCB therapy, there is a need for a safe, potent and short-acting vasodilator. The aim of this study was to compare the acute response to inhaled nitric oxide (NO) and oral high doses of CCB in 33 consecutive patients with PPH. A significant acute vasodilator response was defined by a fall in both mean pulmonary artery pressure and total pulmonary resistance by >20%. Ten patients responded acutely to NO, nine of whom responded acutely to CCB, without any complications. The 23 other patients failed to respond to NO and CCB. In these nonresponders, nine serious adverse events were observed with CCB (38%). There was no clinical or baseline haemodynamic feature predicting acute vasodilator response. Long-term oral treatment with CCB was restricted to the nine acute responders and a sustained clinical and haemodynamic improvement was observed in only six patients. In primary pulmonary hypertension, the acute response rate to high doses of calcium-channel blockers is low (27%). Serious adverse reactions to high doses of calcium-channel blockers during acute testing are frequently observed in nonresponders. It is concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who respond acutely to calcium-channel blockers and may benefit from long-term treatment with these agents.
High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium
Authors: Delcroix M , Kurz X , Walckiers D , Demedts M , Naeije R
Published: January 2003

Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.
Pulmonary hypertensive effects of lung inflation in chronic hypoxia: a study in rats
Authors: Barer GR , Russell PC , Kapeller K
Published: January 2003

Lung inflation was compared in isolated perfused lungs of control (C) and chronically hypoxic (CH) rats; in the latter, there is muscularization and loss of compliance in the pulmonary arterial system. During ventilation hypoxia, high alveolar pressure (Palv) elevated the pulmonary artery pressure (Ppa) less in C than in CH rats; Ppa fell during sustained inflation, rose on deflation, and after inflation hypoxic vasoconstriction was attenuated. Opposite changes took place in CH rats; Ppa often rose during inflation, fell on deflation, and after inflation hypoxic vasoconstriction was enhanced. Inflation also increased Ppa more in CH than C rats during air ventilation. Ppa/Palv relations measured during incremental inflation revealed normoxic tone in "extra-alveolar" vessels in both rat groups, which usually increased during hypoxia. In CH, but not C rats, there was also evidence for constriction in "alveolar" vessels during hypoxia. The effects of inflation were not changed by NO synthase blockade in either rat group. Pulmonary hypertensive effects of inflation in chronically hypoxic rats can be attributed to vascular remodelling.
Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats
Authors: So KL , de Buijzer E , Gommers D , Kaisers U , van Genderen PJ , Lachmann B
Published: January 2003

Paraquat is a weed killer which causes often fatal lung damage in humans and other animals. There is evidence that the pulmonary surfactant system is involved in the pathophysiology of respiratory failure after paraquat intoxication and, therefore, the possible therapeutic effect of intratracheal surfactant administration on gas exchange in rats with progressive lung injury induced by paraquat poisoning was studied. In one group of rats, the time course of the development of lung injury due to paraquat intoxication was characterized. In a second group of rats, 72 h after paraquat intoxication, the animals underwent mechanical ventilation and only those animals in which the arterial oxygen tension/inspiratory oxygen fraction (Pa,O2/FI,O2) decreased to below 20 kPa (150 mmHg) received exogenous surfactant (200 mg x kg(-1) body weight). Within 3 days the rats in group 1 developed progressive respiratory failure, demonstrated not only by impaired gas exchange and lung mechanics but also by increased minimal surface tension and increased protein concentration in bronchoalveolar lavage fluid. In group 2, intratracheal surfactant administration increased Pa,O2/FI,O2 significantly within 5 min (14.4+/-2.4 kPa (108+/-18 mmHg)) to (55.2+/-53 kPa (414+/-40 mmHg)) and sustained this level for at least 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of severe respiratory failure caused by paraquat poisoning.
Breathing and pulmonary surfactant function in mice 24 h after ozone exposure
Authors: Currie WD , van Schaik S , Vargas I , Enhorning G
Published: January 2003

The aim of this study was to determine whether an acute ozone exposure affects breathing, and the ability of pulmonary surfactant to maintain the patency of terminal conducting airways. BALB/c mice were exposed to ozone (1 part per million (ppm)) for 2, 4, 6, and 8 h. They were examined with plethysmography and with bronchoalveolar lavage (BAL) 24 h later. The BAL fluid was analysed for the presence of inflammatory cells and concentrations of proteins and phospholipids. Surfactant in the remaining BAL fluid was concentrated five-times and examined with a capillary surfactometer (CS). The surfactant was then washed with a large volume of saline solution which was removed following centrifugation. Already, after a 2 h ozone exposure, the respiratory frequency increased from 297+/-6 to 386+/-11 breaths x min(-1) (p<0.0001). Pressure amplitude per breath diminished (p<0.001), indicating a reduced tidal volume. A highly significant surfactant dysfunction was observed with the CS (p<0.0001), although phospholipids increased. However, proteins also increased (p<0.0001) and they or other water-soluble inhibitors apparently caused the surfactant dysfunction since, when they were removed with a washing procedure, the surfactant's normal ability to maintain patency was restored. The acute ozone exposure affected breathing and caused an airway inflammation. The inflammatory proteins or other water-soluble inhibitors reduced the surfactant's ability to secure airway patency.
Uptake and degradation of Curosurf after tracheal administration to newborn and adult rabbits
Authors: Alberti A , Pettenazzo A , Enzi GB , Palamidese A , Mapp C , Ventura P , Baritussio A
Published: January 2003

This paper examines the removal from the airways of Curosurf, a commercial surfactant derived from porcine lungs, administered at pharmacological concentrations to newborn or adult animals. Curosurf was labelled by the addition of radioactive dipalmitoyl phosphatidylcholine (DPPC) and administered intratracheally to newborn and adult rabbits at a dose of 200 mg x kg(-1) body weight. The disappearance of DPPC from the airways and its appearance in alveolar macrophages, lung parenchyma, lamellar bodies, serum, liver, kidneys and brain was then studied for 24-48 h. The in vitro degradation of Curosurf DPPC by alveolar macrophages was also studied. During the first 3 h after instillation, large amounts of Curosurf left the airways and became associated with tissue, indicating that it mixed rapidly with the endogenous pools of surfactant. A fraction of administered DPPC became associated with the lamellar bodies, suggesting that Curosurf can be recycled. Curosurf administration did not stop the secretion of endogenous surfactant. Very little intact radioactive DPPC could be recovered at any time in alveolar macrophages, however, macrophages have the ability, in vitro, to degrade Curosurf. Newborn rabbits lose Curosurf from the lungs at a slower rate than adult rabbits. One and two days after instillation, organic extracts from the liver, kidney, brain and serum contained small but measurable amounts of radioactivity. These results indicate that Curosurf rapidly enters the pathways of surfactant metabolism and that alveolar macrophages may play an important role in the catabolism of Curosurf.
Surfactant composition reflects lung overinflation and arterial oxygenation in patients with acute lung injury
Authors: Bersten AD , Doyle IR , Davidson KG , Barr HA , Nicholas TE , Kermeen F
Published: January 2003

Pulmonary surfactant abnormalities have consistently been documented in patients with acute lung injury (ALI), however, there is little evidence directly correlating them to altered respiratory mechanics. To explore this further, surfactant composition was measured in lung aspirate fluid collected on 15 occasions from 10 patients with ALI. The composition was compared with lung aspirate fluid from 11 intubated patients prior to elective cardiac surgery (CS), and bronchoalveolar lavage fluid from 16 normal subjects. In both the ALI and cardiac groups the proportion of disaturated phospholipids (DSP) and phosphatidylcholine was reduced. Plasma levels of surfactant proteins-A and -B (SP-A and -B) were elevated, but were unrelated to alveolar surfactant levels. In the ALI group, and the ALI + CS group, DSP, normalized to the total phospholipid content, sphingomyelin (SPH), and urea, showed strong direct correlations with arterial oxygen tension/inspiratory oxygen fraction (all p < or = 0.01). In the ALI group, normalized DSP was also directly related to the elastance of the positive end-expiratory pressure-induced increase in the end-expiratory lung volume (all p < or = 0.02), and indirect correlations were found with a measure of lung overinflation (%E2; all p < or = 0.01). We conclude that surfactant composition correlates with lung function abnormalities in acute lung injury and cardiac patients, and that both groups had elevated plasma surfactant proteins-A and -B levels, consistent with a concurrent increase in alveolocapillary permeability.
Standardization of ambulatory peak flow monitoring: the importance of recent beta2-agonist inhalation
Authors: Reddel HK , Ware SI , Salome CM , Marks GB , Jenkins CR , Woolcock AJ
Published: January 2003

Standardization of conditions for peak expiratory flow (PEF) monitoring is much more difficult in practice than for laboratory spirometry. Patients are usually asked to record PEF before medication. The aim of this study was to determine the effect of prior bronchodilator use on PEF outcome measures in a clinical trial. Electronic PEF records from 43 subjects with poorly controlled asthma were examined to determine the frequency with which beta2-agonist was inhaled <4 h before PEF measurement, as such PEF are potentially "postbronchodilator". The effect of inclusion of such PEF values on improvement in PEF outcome measures after 8 weeks of inhaled budesonide was calculated. Subjects were asked to record PEF before medication. During run-in, the median frequency of postbronchodilator PEF was 29%, falling to 0% after 8 weeks of budesonide. Inclusion of postbronchodilator PEF led to an overestimation of average morning, evening and daily PEF during run-in (p<0.001). Improvement in these indices with treatment was, therefore, underestimated. Minimum morning PEF expressed as per cent personal best was unaffected. Subjects may not be able to withhold beta2-agonist for 4 h before every peak flow reading. This may change as the level of asthma control changes, leading to a systematic bias in clinical trial end-points or inaccuracy in individual treatment decisions. Simple changes to peak expiratory flow instructions and analysis are proposed.
Fish consumption and respiratory symptoms among young adults in a Norwegian community
Authors: Fluge O , Omenaas E , Eide GE , Gulsvik A
Published: January 2003

The aim of this study was to investigate the relationship between dietary fish consumption and self-reported respiratory symptoms among young adults. A random sample of 4,300 subjects, aged 20-44 yrs, living in Bergen, Norway, received a postal questionnaire on respiratory symptoms, of whom 80% responded. Mean fish consumption was assessed in a food-frequency questionnaire by asking how often the subject consumed units of fish (150 g) during the last year. Average fish consumption was 1.8 units x week(-1). Fish intake of <1 unit x week(-1) was reported by 24%, 41% reported consumption of 1 unit x week(-1) and 35% intake of >1 unit x week(-1). A high fish intake was significantly associated with increasing age after adjusting for smoking. Adjusted for smoking habits, the prevalence of "cough at night" and "chest tightness" showed a decreasing trend with increasing fish consumption (p<0.05), while such a trend for "wheeze" was demonstrated only in smokers (p=0.008 for interaction). In logistic regression models (adjusting for age, sex, body mass, smoking habits and occupational exposure) fish consumption (three categories) was not significantly associated with "wheeze", "chest tightness", "breathless at night" or "asthma attack", although the odds ratios (OR) were consistently less than 1 (except for "asthma attack"). Fish consumption was of borderline significance as a protective factor of "cough at night", OR = 0.86 (95% confidence interval: 0.76-0.97) but in stratified analyses only in smokers. Subjects reporting very high levels of fish consumption (>14 units x week(-1)) did not have lower prevalences of respiratory symptoms. In conclusion, among young Norwegian adults, with a relatively low prevalence of asthma and an overall high fish intake, fish consumption was not a significant predictor of four out of five respiratory symptoms.
Nebulized magnesium sulphate versus nebulized salbutamol in acute bronchial asthma: a clinical trial
Authors: Mangat HS , D'Souza GA , Jacob MS
Published: January 2003

Intravenous magnesium sulphate (MgSO4) has successfully been used in the treatment of acute asthma. The present study investigated the efficacy of nebulized MgSO4 as a bronchodilator in acute asthma as compared to nebulized salbutamol. This was a randomized, double-blind, controlled clinical trial. Asthmatics aged 12-60 yrs in acute exacerbation, with a peak expiratory flow (PEF) <300 L x min(-1), not having taken bronchodilators and not requiring assisted ventilation were included. Patients were randomized to receive treatment with serial nebulizations of either 3 mL (3.2% solution, 95 mg) MgSO4 solution or 3 mL (2.5 mg) salbutamol solution. All patients were also given 100 mg hydrocortisone i.v., and were monitored continuously for 2 h after which they were given supplemental treatment (if and when needed) and either discharged or admitted. Fischl index, PEF improvements (in % predicted) and admission rates were the outcome variables. Thirty-three patients were studied. Fischl score improvement was comparable and significant in both groups (4.31 to 0.43 in the MgSO4 group and 4.29 to 0.76 in the salbutamol group). The increase in PEF was statistically significant and comparable in both groups (by 35% pred in the MgSO4 and by 42% pred in the salbutamol group). Two patients warranted admission in the salbutamol group and one in the MgSO4 group. Nebulized MgSO4 had a significant bronchodilatory effect in acute asthma. This effect was not significantly different from that of nebulized salbutamol.
Evidence for mast cell activation during exercise-induced bronchoconstriction
Authors: O'Sullivan S , Roquet A , Dahlen B , Larsen F , Eklund A , Kumlin M , O'Byrne PM , Dahlen SE
Published: January 2003

Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced bronchoconstriction by measuring urinary metabolites of mast cell mediators. Twelve nonsmoking subjects with mild asthma and a history of exercise-induced bronchoconstriction exercised on a stationary bicycle ergometer for 5 min at 80% maximum work load. Pulmonary function was monitored and urine was collected before and 30 and 90 min after the provocation. The urinary concentrations of the mast cell markers 9alpha,11beta-prostaglandin (PG)F2 and Ntau-methylhistamine, as well as leukotriene E4 (LTE4) were determined by immunoassay. Seven of the 12 subjects (responders) experienced bronchoconstriction (>15% fall in the forced expiratory volume in one second) following exercise, whereas the pulmonary function of the remaining five subjects (nonresponders) remained stable. The urinary excretion (mean+/-SE) of 9alpha,11beta-PGF2 in the responders increased significantly compared with the nonresponders at 30 (77.1+/-14.4 versus 37.2+/-5.6; p<0.05) and 90 min (79.3+/-8.6 versus 40.4+/-8.5, p<0.05) after exercise challenge. The urinary excretion of Ntau-methylhistamine and LTE4 was not significantly different between the two groups at 30 or 90 min after exercise. The findings represent the first documentation of increased urinary levels of 9alpha,11beta-prostaglandin F2 in adults following exercise challenge and provides clear evidence for mast cell activation during exercise-induced bronchoconstriction in asthmatics.
Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis
Authors: Plit ML , Anderson R , Van Rensburg CE , Page-Shipp L , Blott JA , Fresen JL , Feldman C
Published: January 2003

Patients who have completed a treatment for severe pulmonary tuberculosis (TB) are often left with severe respiratory disability. There have been few prospective studies assessing the effect of treatment on lung function in such patients. The influence of antimicrobial chemotherapy on lung function was investigated over a six month period in patients with newly diagnosed pulmonary TB to test the hypothesis that treatment improves lung function, as well as to identify factors that may influence lung function outcome. Seventy-six patients were recruited into the study, of whom 74 completed the treatment programme. Forty-two were current smokers and 13 seropositive for the human immunodeficiency virus. Improvement in lung function occurred in 54% of patients, but residual airflow limitation or a restrictive pattern was evident in 28% and 24% of patients, respectively. The extent of lung infiltration (radiographic score) both at the outset and after chemotherapy was significantly and negatively related to forced expiratory volume in one second (FEV1) (% pred) (r=-0.41, and r=-0.46, respectively). The post-treatment serum C-reactive protein and alpha1-protease inhibitor levels were negatively associated with FEV1 (% pred) (r=-0.30 and r=-0.35, respectively). These findings demonstrate that, while antimicrobial chemotherapy may lead to improved lung function in patients with pulmonary tuberculosis, a large proportion of patients has residual impairment. The most significant factor influencing post-treatment lung function status, as measured by forced expiratory volume in one second (% predicted), is the pretreatment and post-treatment radiographic score, which acts as a marker of the extent of pulmonary parenchymal involvement in tuberculosis.
Thoracic infection caused by Streptococcus milleri
Authors: Porta G , Rodriguez-Carballeira M , Gomez L , Salavert M , Freixas N , Xercavins M , Garau J
Published: January 2003

The objective of this study was to increase our understanding of the importance of members of the Streptococcus milleri (SM) group as respiratory pathogens, by studying the epidemiological and clinical features of thoracic infections caused by this group and comparing the epidemiology and prognosis of empyema caused by SM with cases of pneumococcal aetiology. The clinical histories and microbiology reports were reviewed in 27 cases of thoracic infection caused by SM over a period of 8 yrs. Cases of pneumococcal empyema that occurred during the same period were also analysed. Diagnoses were made of cases of empyema, including six with pneumonia and one with pulmonary abscess, three cases of pneumonia and two of mediastinitis. In 17 cases, SM was the only pathogen isolated. There was a history of instrument or surgical procedures on the digestive or respiratory tract in 59%. Secondary bacteraemia was documented in three cases. The treatment administered, a combination of antibiotics and surgery, was successful in 22 of 27 (81%) of cases. All strains were susceptible to penicillin. When the characteristics of the empyemas caused by monomicrobial SM infection were compared with those of pneumococcal aetiology from the same period of study, significant differences were found with respect to age, origin of the infection and the need for surgery. In conclusion, thoracic infections caused by Streptococcus milleri are largely pleural. They are polymicrobial in one-third of cases, commonly acquired in hospital and, in most patients, associated with major surgery and/or surgical procedures of the respiratory or digestive tract. The empyema frequently requires thoracotomy for complete resolution.
Randomized controlled trial of pulmonary rehabilitation in severe chronic obstructive pulmonary disease patients, stratified with the MRC dyspnoea scale
Authors: Wedzicha JA , Bestall JC , Garrod R , Garnham R , Paul EA , Jones PW
Published: January 2003

This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation. In this randomized, controlled study, 126 patients with chronic obstructive pulmonary disease (COPD) were stratified for dyspnoea using the Medical Research Council (MRC) dyspnoea score into MRC3/4 (Moderate) (n=66) and MRC 5 (Severe) dyspnoeic (n=60) groups. The patients were randomly assigned to an eight week programme of either exercise plus education (Exercise group) or education (Control group). Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting. Severely dyspnoeic patients were all treated at home. Those in the Exercise group received an individualized training programme. There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group, who received exercise training; baseline (mean+/-SEM) 191+/-22 m, post-rehabilitation 279+/-22 m (p<0.001). There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise. Neither group of control patients improved. Health status, assessed by the Total Chronic Respiratory Disease Questionnaire score, increased in the moderately dyspnoeic patients receiving exercise from 80+/-18 to 95+/-17 (p<0.0001) after rehabilitation. Much smaller changes were seen in the other three groups. Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea.