bluuebunny/crossref_metadata_2025 huggingface dataset:
Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival
Authors: Liu Hongtao , Ma Yingyu , Cole Shawn M. , Zander Christopher , Chen Kun-Hung , Karras Jim , Pope Richard M.
Published: June 2003

The Bcl-2 family member Mcl-1 is essential for macrophage survival. However, the mechanisms that contribute to the expression of Mcl-1 in these cells have not been fully characterized. The present study focused on the role of signal transducer and activator of transcription 3 (STAT3) in regulation of Mcl-1 in macrophages. Sodium salicylate (NaSal) treatment induced apoptotic cell death in primary human macrophages in a dose- and time-dependent fashion. Incubation with NaSal resulted in the loss of mitochondrial transmembrane potential, the release of cytochromecand second mitochondria-derived activator of caspase/direct IAP binding protein with low pH of isoelectric point (pI) from the mitochondria, and the activation of caspases 9 and 3. Western blot analysis and reverse transcription—polymerase chain reaction demonstrated that NaSal down-regulated the expression of Mcl-1. Electrophoretic mobility shift assay and Western blot analysis for phosphorylated STAT3 demonstrated that STAT3 was constitutively activated in macrophages and that this STAT3 activation was suppressed by NaSal. The activation of STAT3 in macrophages was dependent on Ser727 phosphorylation, in the absence of detectable Tyr705phosphorylation. Ectopic expression of STAT3 in murine RAW264.7 macrophages rescued the inhibition of Mcl-1 promoter-reporter gene activation and the cell death induced by NaSal treatment, while a dominant-negative STAT3 resulted in cell death. To confirm its role in primary macrophages, STAT3 antisense (AS) oligodeoxynucleotides (ODNs) were employed. STAT3 AS, but not control, ODNs decreased STAT3 and Mcl-1 expression and resulted in macrophage apoptosis. These observations demonstrate that the STAT3-mediated expression of Mcl-1 is essential for the survival of primary human in vitro differentiated macrophages. (Blood. 2003;102:344-352)
Result of high-dose imatinib mesylate in patients with Philadelphia chromosome—positive chronic myeloid leukemia after failure of interferon-α
Authors: Cortes Jorge , Giles Francis , O'Brien Susan , Thomas Deborah , Garcia-Manero Guillermo , Rios Mary Beth , Faderl Stefan , Verstovsek Srdan , Ferrajoli Alessandra , Freireich Emil J. , Talpaz Moshe , Kantarjian Hagop
Published: June 2003

Imatinib at 400 mg daily is effective in chronic-phase chronic myeloid leukemia (CML) after interferon failure, although only a few patients achieve a molecular remission. We investigated whether higher doses of imatinib may be more effective. Thirty-six patients with chronic-phase CML after failure on interferon-α were treated with 400 mg imatinib twice daily. Median time from diagnosis was 25 months (range, 10-135 months); 4 patients (11%) had clonal evolution. All 11 patients with active disease achieved complete hematologic response. Excluding patients with fewer than 35% Ph-positive metaphases before the start of therapy, 19 (90%) of 21 evaluable patients achieved a major cytogenetic response. Of 27 evaluable patients, 24 (89%) achieved a complete cytogenetic response. Quantitative polymerase chain reaction was performed in bone marrow every 3 months. Of 32 evaluable patients, 18 (56%) showed BCR-ABL/ABL percentage ratios lower than 0.045%, including 13 (41%) with undetectable levels. With a median follow-up of 15 months, all patients were alive in chronic phase. Toxicities were similar to those reported with standard dose; 71% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induces complete cytogenetic responses in most patients with chronic-phase CML after interferon failure. This is accompanied by a high rate of molecular remission. (Blood. 2003;102:83-86)
Ventilatory and pulmonary vascular response to hypoxia and susceptibility to high altitude pulmonary oedema
Authors: Hohenhaus E , Paul A , McCullough RE , Kucherer H , Bartsch P
Published: June 2003

Reduced tolerance to high altitude may be associated with a low ventilatory and an increased pulmonary vascular response to hypoxia. We therefore, examined whether individuals susceptible to acute mountain sickness (AMS) or high altitude pulmonary oedema (HAPE) could be identified by noninvasive measurements of these parameters at low altitude. Ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) at rest and during exercise, as well as hypoxic pulmonary vascular response (HPVR) at rest, were examined in 30 mountaineers whose susceptibility was known from previous identical exposures to high altitude. Isocapnic HVR expressed as difference in minute ventilation related to difference in arterial oxygen saturation (delta V'E/ delta Sa,O2) (L.min-1/%) was significantly lower in subjects susceptible to HAPE (mean +/- SEM 0.8 +/- 0.1; n = 10) compared to nonsusceptible controls (1.5 +/- 0.2; n = 10), but was not significantly different from subjects susceptible to AMS (1.2 +/- 0.2; n = 10). Hypercapnic ventilatory response was not significantly different between the three groups. Discrimination between groups could not be improved by measurements of HVR during exercise (50% maximum oxygen consumption (V'O2,max)), or by assessing ventilation and oxygen saturation during a 15 min steady-state exercise (35% V'O2,max) at fractional inspiratory oxygen (FI,O2) of 0.14. Pulmonary artery pressure (Ppa) estimated by Doppler measurements of tricuspid valve pressure at an FI,O2 of 0.21 and 0.12 (10 min) did not lead to a further discrimination between subjects susceptible to HAPE and AMS with the exception of three subjects susceptible to HAPE who showed an exaggerated HPVR. It is concluded that a low ventilatory response to hypoxia is associated with an increased risk for high altitude pulmonary oedema, whilst susceptibility to acute mountain sickness may be associated with a high or low ventilatory response to hypoxia. A reliable discrimination between subjects susceptible to high altitude pulmonary oedema and acute mountain sickness with a low ventilatory response to hypoxia is not possible by Doppler echocardiographic estimations of hypoxic pulmonary vascular response.
Thrombolytic therapy of right heart emboli-in-transit
Authors: Jessurun GA , Brugemann J , Hamer JP , Romer JP , Lie KI
Published: June 2003

Currently, no consensus exists for the appropriate treatment of echocardiographically diagnosed mobile right heart masses giving rise to a high suspicion of migrant thromboembolism in patients with pulmonary embolism. This may lead to unnecessary delay in the implementation of the most appropriate treatment for these patients. Several earlier studies have supported the beneficial role of thrombolytic therapy. We report on an additional two patients with mobile right heart thromboemboli, refractory to systemic anticoagulation, who recovered quickly after initiation of thrombolytic therapy.
Angiotensin II potentiates methacholine-induced bronchoconstriction in human airway both in vitro and in vivo
Authors: Millar EA , Nally JE , Thomson NC
Published: June 2003

Angiotensin II levels are elevated in patients with acute severe asthma. In addition, intravenous angiotensin II causes bronchoconstriction in mild asthmatic patients. In the present study, we examined the effects of this hormone on bronchi in vitro and its interaction with the cholinergic agonist methacholine both in vivo and in vitro. Contractions of rings of human bronchi were measured isometrically. Concentration-response curves were obtained to angiotensin II and to methacholine in the presence and absence of angiotensin II. In addition, seven asthmatic patients with mild bronchial hyperreactivity to methacholine received placebo, angiotensin II, 1 or 2 ng.kg-1.min, by infusion, followed by methacholine challenge. Forced expiratory volume in one second (FEV1) values were measured at baseline, at the end of the infusion and during methacholine challenge. Angiotensin II alone in vitro evoked small contractions of human bronchi ( < 0.25 g wt). Pre-incubation with low concentrations of angiotensin II significantly enhanced contractions to methacholine. In mild asthmatic patients, angiotensin II alone evoked no change in baseline FEV1 values at the levels studied. Compared to placebo, angiotensin II 2 ng.kg-1.min, but not 1 ng.kg-1.min, evoked a significant increase in bronchial reactivity to methacholine. Angiotensin II in subthreshold concentrations enhances methacholine-evoked bronchoconstrictions both in human in vitro and in mild asthmatic patients in vivo. Our findings suggest a novel role for angiotensin II as a putative mediator in asthma.
High altitude exposure reduces bronchial responsiveness to hypo-osmolar aerosol in lowland asthmatics
Authors: Allegra L , Cogo A , Legnani D , Diano PL , Fasano V , Negretto GG
Published: June 2003

It is well-known that many patients with asthma undergo clinical improvement during a stay at high altitude. At high altitude, the atmospheric and climatic conditions (such as hypoxia, cold and dry air inhalation) could modify the bronchial responsiveness in asthmatics. Our study was designed to assess the difference in bronchial responsiveness to hypotonic aerosol between sea level and high altitudes in nonresident asthmatic subjects. The results were obtained during two mountaineering expeditions above 4,000 m i.e. at 4,559 m on Mt Rosa, Italy; and at 5,050 m near the Mt Everest base camp in Nepal. Eleven mild asthmatics performed standard bronchial challenges with ultrasonically nebulized distilled water (5 min inhalation, delivery 2 mL-min-1) at sea level and after staying at least 72 h at the above mentioned altitudes. The decrease in forced expiratory volume in one second (FEV1) from baseline was used as index of bronchial response. There was no significant difference in pre-challenge FEV1 between sea level and high altitude in either study. However, the bronchoconstriction response to ultrasonically nebulized distilled water was significantly reduced at high altitude in both studies. At sea level the mean FEV1 decrease was 22.2% (range 15-35%), whereas as the maximal altitude it was 6.7% (range 2-11%). Our results indicate that there is a reduction in bronchial responsiveness to hypoosmolar aerosol at high altitude. This suggests that atmospheric and climatic conditions, or physiological adaptations, via mediators such as atrial natriuretic peptide, are beneficial to patients with asthma at high altitude.
Reduced dose salbutamol in comparison with standard dosage for symptom relief in asthma
Authors: Yates DH , Peters MJ , Keatings V , Thomas PS , Barnes PJ
Published: June 2003

Regular treatment with beta 2-agonists has been reported to be associated with an increase in risk of asthma death or near death, and with a deterioration in asthma symptom control. Low-dose beta 2-agonists provide effective bronchodilatation and bronchoprotection, even though maximal bronchodilatation is not achieved, and they may offer a better safety profile. In a double-blind, randomized,, cross-over study, we evaluated the efficacy of low-dose salbutamol metered-dose inhaler (50 micrograms.puff-1), used over a period of 2 weeks, compared with a standard dose (100 micrograms.puff-1) in control of asthma symptoms in 20 moderately severe asthmatic subjects using inhaled glucocorticosteroid therapy. Asthma control was assessed by symptom scores, peak flow rates, spirometry, inhaler usage and, where possible, by bronchial responsiveness to methacholine. Despite a 46% reduction in mean weekly salbutamol dosage, mean forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow (PEF), PEF variability, dose of methacholine provoking a 20% decrease in FEV1 (PC20) (n=9), and symptom scores showed no difference between low-dose and standard inhaler treatment periods. Low-dose inhaler administration resulted in a small but significant increase in number of inhaler actuations. Low-dose salbutamol metered-dose inhaler may, thus, be useful for control of symptoms in moderately severe asthma. This strategy could be used to achieve a reduction in total beta 2-agonist usage, which may minimize any potential for adverse effects.
Overnight protection by inhaled salmeterol on exercise-induced asthma in children
Authors: Carlsen KH , Roksund O , Olsholt K , Nja F , Leegaard J , Bratten G
Published: June 2003

The main aim of the present study was to evaluate whether inhaled salmeterol given in the evening protected against exercise-induced asthma the next morning. Twenty three children (12 males and 11 females) with a mean age of 11 yrs and with exercise-induced asthma participated in a double-blind, randomized, placebo-controlled study. The children inhaled salmeterol 25 micrograms, salmeterol 50 micrograms and placebo by Diskhaler at 10 p.m. on 3 separate days. Next morning, half of the children ran on a motor-driven treadmill for 6 min at submaximal load at 8 a.m. and the remainder at 10 a.m. Lung function was measured by maximal expiratory flow-volume loops before running, immediately after, and 3, 6, 10 and 15 min after running. The mean maximum reduction in forced expiratory volume in one second (FEV1) after treadmill run was 34% before inclusion in the study. Mean maximum fall in FEV1 was significantly greater after placebo: 30% (23-36) 95% confidence interval) than after salmeterol 25 micrograms: 19% (12-23) or salmeterol 50 micrograms: 18% (12-25). In addition to the reduced postexercise bronchoconstriction, pre-exercise lung function (FEV1) was significantly higher both after salmeterol 25 micrograms: 2.4 L.s-1 (2.1-2.7) and salmeterol 50 micrograms: 2.5 L.s-1 (2.2-2.8) than after placebo: 2.2 L.s-1 (1.9-2.5). No significant differences in pre- and postexercise lung function were found between children tested at 8 or 10 a.m., or in relation to salmeterol dosage. Thus, inhaled salmeterol 25 and 50 micrograms offered similar overnight protection against exercise-induced asthma and improved baseline lung function in the morning as compared to placebo.
Asthma medications and disease exacerbations: an epidemiological study as a method for asthma surveillance
Authors: Van Ganse E , van der Linden PD , Leufkens HG , Herings RM , Vincken W , Ernst P
Published: June 2003

Recent experimental and epidemiological studies have suggested that outcomes of asthma are significantly influenced by treatment patterns. This study was conducted in order to investigate the links between treatment patterns in asthmatics and occurrence of disease exacerbations. We performed a nested case-control study in a cohort of 680 asthmatics identified between 1986 and 1991 in a drug dispensing database. After validation in a pilot study, the intermittent use of oral corticosteroids was used as a proxy for asthma exacerbations. Cases with an exacerbation (n=133) were pair-wise matched with controls. The type of medications used for the usual treatment of asthma were examined in relation to the risk of asthma exacerbation. The use of oral xanthines and inhaled fenoterol but not of inhaled salbutamol, corticosteroids, cromoglycate and ipratropium bromide was associated with an increased probability of asthma exacerbation. Within the cohort, the proportion of subjects dispensed inhaled corticosteroids rose from 12 to 27% between 1986 and 1991. The proportion of subjects using inhaled bronchodilators without inhaled corticosteroids also decreased over this period of time. The identification of markers of asthma exacerbations made it possible to link the probability of adverse outcome risk for such exacerbations with treatment patterns. This method could be useful in further development of asthma surveillance using drug dispensing databases.
IgE-induced passive sensitization of human isolated bronchi and lung mast cells
Authors: Tunon de Lara JM , Okayama Y , Savineau JP , Marthan R
Published: June 2003

Passive sensitization of human isolated lung with serum from atopic asthmatic patients provides an opportunity to study the link between airway hyper-responsiveness and the allergic process. To directly demonstrate the role of immunoglobulin E (IgE) in the effect of the atopic serum, we have compared the effect of passively sensitizing both human bronchi and isolated lung mast cells with either serum from atopic asthmatic patients or human monoclonal IgE. Peripheral bronchi ( < 5 mm in internal diameter) were dissected out from human lung obtained at thoractomy and isometric contraction was studied in response to a variety of immunological stimuli according to the sensitization protocol. Mast cells were also isolated from human lung and histamine release was measured under similar experimental conditions. A contractile response was elicited by either the specific antigen or anti-IgE (0.6-600 ng.mL-1) but not anti-immunoglobulin G (IgG) 0.2-20 micrograms.mL-1) in airways sensitized with atopic serum (total IgE concentration of approximately 1,000 international units (IU).mL-1). The maximal contractile response to anti-IgE was 75 +/- 22% of the response to 1 mM acetylcholine. Similarly, anti-IgE released histamine from isolated lung mast cells sensitized with atopic serum up to 22.4 +/- 2% of total histamine measured within mast cells. When isolated airways or mast cells were sensitized with human monoclonal IgE (1,000 IU.mL-1), response to anti-IgE in terms of contractile response or histamine release, respectively, were not significantly different from those obtained following passive sensitization with atopic serum. Finally, the bronchial contractile response to anti-IgE depended not only on the concentration of anti-IgE but also on that of IgE (300-2,000 IU.mL-1) used to sensitize the airways. These results indicate that the effect of antigen or anti-IgE in peripheral bronchi passively sensitized with atopic serum is mimicked when sensitization is carried out directly with human monoclonal IgE.
Intrasubject variability in airway inflammation sampled by bronchoalveolar lavage in stable asthmatics
Authors: Ward C , Gardiner PV , Booth H , Walters EH
Published: June 2003

Despite the increasing complexity of bronchoalveolar lavage (BAL) studies in asthmatics there are few published data concerning the variability of inflammatory parameters measured using this technique. We studied the intrasubject variability of cellular and solute parameters in 20 clinically stable, symptomatic, mild-to-moderate asthmatics, in repeat 180 mL BAL procedures performed 1 month apart. During the study, there was no change in disease activity or medication. Mean (SD) forced expiratory volume in one second (FEV1) was 3.2 (1.09) L at the first BAL and 3.05 (0.98) L at the second. The geometric mean dose of methacholine provoking a 20% decrease in FEV1 (PD20) was 23 micrograms (range 2-1,170 micrograms) at the first BAL and 28 micrograms (range 2-400 micrograms) at the second. There was considerable variability in the BAL cellular and solute parameters measured over the two procedures. Estimates of power calculated for subsequent studies involving this type of subject group were made from the observed variability. Sample sizes of less than 15 mean that differences have to be large in order to be detected in repeat BAL samples. However, there is little improvement in the power of BAL studies for sample sizes greater than 20, indicating that there is little gain in recruiting more than this number of subjects. Thus, our study indicates that although studies of the pathophysiology underlying asthma using BAL require considerable commitment, they are practicable.
Effects of IL-2 treatment on different compartments of the irradiated rat lung analysed by bronchoalveolar lavage and lung tissue morphology
Authors: Yi-Qing C , Bjermer L , Frojd O , Nettelbladt O , Karlsson-Parra A , Henriksson R
Published: June 2003

In recent years, interleukin-2 (IL-2) has been used as an immunomodulatory agent in the treatment of various malignant tumours. However, this treatment has been limited by serious side-effects, including toxic reactions in the lung. The effects of IL-2 treatment on inflammatory cell populations in the normal and irradiated rat lung were investigated in this study. IL-2 was continuously administered as a subcutaneous infusion over a 6 week study period. Irradiation was given in a single dose (25 Gy) the day after starting IL-2 treatment. Evaluation with bronchoalveolar lavage fluid (BALF) analysis and lung tissue morphology was made 6 weeks after irradiation. In nonirradiated rats, IL-2 treatment induced significant increases in the total number of inflammatory cells in the perivascular, interstitial and peribronchial tissues as well as in the alveolar space. These increases were not reflected in BALF; on the contrary, a significant decrease of the total numbers of inflammatory cells was found in BALF. Irradiation alone caused a more pronounced inflammatory response was significant increases of all inflammatory cells in all lung compartments, which was also reflected in BALF. Concomitant treatment with IL-2 and irradiation induced an enhanced accumulation of inflammatory cells in the perivascular and peribronchial tissues compared with irradiation alone. Thus, both irradiation and IL-2 treatment induce inflammatory reactions in the lung, but there were signs of synergistic effects seen in this study. Furthermore, the results also emphasize the difficulties in making sophisticated conclusions from BALF analyses alone.
Diagnosis of pulmonary lymphangioleiomyomatosis by HMB45 in surgically treated spontaneous pneumothorax
Authors: Tanaka H , Imada A , Morikawa T , Shibusa T , Satoh M , Sekine K , Abe S
Published: June 2003

Pulmonary lymphangioleiomyomatosis (PLAM) is a rare disease with poor prognosis, characterized by an abnormal proliferation of smooth muscle. The patients are females and recurrent pneumothorax is a frequent complication. HMB45 is a monoclonal antibody with specific immunoreactivity for malignant melanoma. Recently, it was reported that some of the smooth muscle cells in PLAM had reactivity for HMB45. The aim of this study was to assess the sensitivity and specificity of HMB45 for the diagnosis of PLAM in cystic pulmonary diseases that cause recurrent pneumothorax. We compared immunoreactivity of the specimens obtained by open lung biopsy at surgical resection of bullae in 72 patients. The specimens of five females with PLAM, one female with suspected PLAM, 49 patients with primary spontaneous pneumothorax (19 females and 30 males), four with pulmonary eosinophilic granuloma (2 females and 2 males), seven with pulmonary emphysema (7 males), and six with idiopathic pulmonary fibrosis with apical bullous change (2 females and 4 males) were stained with HMB45 and anti-smooth muscle actin. All PLAM cases had HMB45 positive cells, which also stained with anti-smooth muscle actin. The biopsy specimens of a PLAM suspected case also stained with HMB45. None of the specimens from other diseases reacted with HMB45. HMB45 appears to provide a highly specific and highly sensitive diagnosis for PLAM in females. It may also be useful in patients with subtle smooth muscle proliferation. where the diagnosis of PLAM is difficult to confirm by conventional histological examination.
Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome
Authors: Cremona G , Higenbottam TW , Mayoral V , Alexander G , Demoncheaux E , Borland C , Roe P , Jones GJ
Published: June 2003

The hypoxaemia of hepatopulmonary syndrome, seen in severe chronic liver dysfunction, occurs as a result of precapillary pulmonary arterial dilatation and arteriovenous communications. These abnormalities contribute to the mismatch between ventilation and perfusion, and the right to left blood flow shunting. Nitric oxide (NO) is a powerful vasodilator concerned with the regulation of pulmonary vascular tone in man. Using a chemiluminescence analyser, we have measured endogenously produced NO in the exhaled air of three patients with the hepatopulmonary syndrome, six normoxaemic cirrhotic patients and six healthy volunteers. The subjects breathed NO-free air throughout the measurements. The molar rate of production of exhaled NO was raised almost threefold in the patients with hepatopulmonary syndrome compared with normal volunteers and with normoxaemic cirrhotic patients. Hypoxia per se, achieved in the normal volunteers by breathing a hypoxic gas mixture, reduced rather than increased the exhaled NO. One hepatopulmonary syndrome patient received an orthotopic liver transplant and achieved normoxaemia after 3 months. The exhaled NO also returned to normal. Increased pulmonary production of NO could contribute to the development of the hepatopulmonary syndrome.
Repeatability of airway deposition and tracheobronchial clearance rate over three days in chronic bronchitis
Authors: Ericsson CH , Svartengren K , Svartengren M , Mossberg B , Philipson K , Blomquist M , Camner P
Published: June 2003

Previous investigations on tracheobronchial clearance in chronic bronchitis or chronic obstructive pulmonary disease (COPD) have usually referred to measurements during a short time-period, i.e. a few hours. The purpose of this study, therefore, was to study regional particle deposition and tracheobronchial clearance during 72 h. In 14 patients with chronic bronchitis clearance of 111In-labelled 3.6 micrograms Teflon particles and lung function were measured on two occasions, with an interval of 2 weeks. Lung retention of test particles was measured at 0, 24, 48 and 72 h using a profile scanner. The weight of expectorated sputum samples was measured after the two clearance measurements. The particle retentions at all time-points were reproducible, as seen from the two measurements ( r > 0.90). The fast clearance phase was completed within 72 h. No correlation between sputum volume and clearance was seen. There was a significant negative correlation between airway resistance and the 72 h retention (r= -0.66), and an even better correlation between specific airway resistance and the 72 h retention (r = -0.82), indicating more central deposition in obstructed airways. There was no significant correlation between lung function tests reflecting smaller airways and the 72 h retentions. Deposition data agreed well with theoretical calculations and experimental data in healthy subjects. In spite of earlier findings that mucociliary transport is usually severely impaired in chronic bronchitis and COPD, the present results indicate that overall tracheobronchial mucus clearance in these patients is fairly effective, probably due to a productive cough. Alveolar deposition may be estimated by measurements of the 72 h retention in subjects with chronic obstructive pulmonary disease. The 72 h retention is dependent mainly on the calibre of larger airways. The present method of studying airway clearance during 3 days is highly reproducible.
Efficacy of noninvasive CPAP in COPD with acute respiratory failure
Authors: Goldberg P , Reissmann H , Maltais F , Ranieri M , Gottfried SB
Published: June 2003

Dynamic hyperinflation and the development of intrinsic positive end-expiratory pressure (PEEPi) are commonly observed in patients with severe chronic obstructive pulmonary disease (COPD) in acute respiratory failure. Previous studies have shown that externally applied PEEP reduces PEEPi and its adverse effects in mechanically-ventilated COPD patients. The purpose of this study was to determine the effects of graded amounts of continuous positive airway pressure (CPAP) on the degree of inspiratory effort, pattern of breathing, gas exchange, and level of dyspnoea in a group of spontaneously breathing, nonintubated COPD patients in acute hypercapnic respiratory failure. Ten COPD patients admitted to the intensive care unit in acute hypercapnic respiratory failure were studied. Inspiratory effort was measured by the tidal excursions of oesophageal (Poes) and transdiaphragmatic (Pdi) pressure. Inspiratory effort and both the pressure-time product for the diaphragm (integral of Pdi-dt) and for the inspiratory muscles (integral of Poes.dt) were measured during the application of 5, 7.5, and 10 cmH2O of CPAP. Dyspnoea, gas exchange and pattern of breathing were also assessed. Inspiratory effort and the pressure-time product both for the diaphragm and the inspiratory muscles fell significantly with CPAP in a dose-dependent fashion. Both the pattern of breathing and level of dyspnoea improved with CPAP. End-expiratory lung volume remained stable at the lower levels of CPAP, with only modest increases at the higher levels. Arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2) either improved or remained stable with CPAP. We conclude that the noninvasive application of CPAP to spontaneously breathing patients with severe COPD in acute respiratory failure decreases inspiratory effort and dyspnoea whilst improving breathing pattern. It is conceivable that the early institution of CPAP in this setting may obviate the need for intubation and conventional mechanical ventilation.
Comparative effects of pressure support ventilation and intermittent positive pressure breathing (IPPB) in non-intubated healthy subjects
Authors: Mancebo J , Isabey D , Lorino H , Lofaso F , Lemaire F , Brochard L
Published: June 2003

We compared the efficacy of three devices delivering assisted non-invasive ventilation with different working mechanisms, during room air breathing and during CO2-induced hyperventilation. In seven healthy volunteers, breathing pattern, respiratory muscle activity and comfort were assessed: during unassisted spontaneous breathing through a mouth-piece (SB); during assisted breathing with a device delivering inspiratory pressure support (IPS); and with two devices delivering intermittent positive pressure breathing (IPPB), the Monaghan 505 (IPPB1), and the CPU 1 ventilator (IPPB2). All three devices were set at 10 cmH2O of maximal pressure. During room air breathing, the work of breathing expressed as power, was significantly greater with the two IPPB devices than with the two other modes (IPPB1 and IPPB2 7.3 +/- 5.2 and 7.2 +/- 6.2 J.min-1, respectively, versus SB and IPS 2.4 +/- 0.7 and 2.3 +/- 3.3 J.min-1, respectively). The difference did not reach the statistical significance for the pressure-time product (PTP). Discomfort was also greater during the IPPB modes. During CO2-induced hyperventilation, considerable differences in power of breathing were found between the two IPPB devices and the other two modes. The PTP was also much higher with IPPB. Transdiaphragmatic pressure was significantly smaller during IPS than during the three other modes (IPS 18 +/- 2.6 cmH2O versus SB 22 +/- 2.6, IPPB1 32 +/- 5.2, and IPPB2: 28 +/- 5.2). Maximal discomfort was observed during the IPPB modes and was correlated with the magnitude of transdiaphragmatic pressure (r = 0.60). Despite similarities in their operational principles, IPS and IPPB had very different effects on respiratory muscle activity in healthy non-intubated subjects. IPPB machines not only failed to reduce patient's effort but also induced a significant level of extra work by comparison to spontaneous ventilation at ambient pressure. Great caution is, therefore, needed in the use of patient-triggered devices for non-intubated patients with acute respiratory failure.
Detection of flow limitation during tidal breathing by the interruptor technique
Authors: Hage R , Aerts JG , Verbraak AF , van den Berg B , Bogaard JM
Published: June 2003

In patients with airflow obstruction, flow limitation can be established in various ways. Using body plethysmography, flow limitation is assumed when expiratory flow decreases whilst alveolar pressure increases at the same time. During forced expiration, flow limitation can be established by means of the flow interruptor technique; flow limitation is assumed when, after release of an occlusion, a spike flow superimposed on the ongoing alveolar flow (delta peak flow) is detected. In this study, the flow interruptor technique was applied to detect flow limitation during tidal breathing. The results were compared to those obtained with the body plethysmograph. The expiratory flow pattern, post-interruption, was analysed in 33 subjects; 11 patients with airflow obstruction and flow limitation established with the body plethysmograph (AO+); 11 patients with airflow obstruction without flow limitation (AO-); and 11 healthy volunteers. Mean spike areas were 27.6 +/- 18.3, 4.6 +/- 2.3 and 3.4 +/- 2.0 mL for the AO+, AO- and control group, respectively, showing a highly significant difference between the AO+ patients and the other groups. Also, significantly higher delta peak flows were found in the AO+ patients compared to the other groups. No differences in delta peak flows or spike areas could be established between patients without flow limitation and controls. We conclude that the interruptor technique may be a useful means of assessing flow limitation during tidal breathing.
Mechanism of theophylline-induced inotropic effects on foreshortened canine diaphragm
Authors: Gayan-Ramirez G , Janssens S , Himpens B , Decramer M
Published: June 2003

The mechanisms of theophylline-induced inotropic effects at shorter diaphragm length have not yet been explored. We wondered whether the greater inotropic effects of the drug at shorter diaphragm length might result from an effect on intracellular calcium level. Forty pairs of diaphragm bundles were stimulated at 70% of optimal length in the presence of either verapamil (10(-5)M), calcium-free Krebs solution (buffered or not with 2 mM ethylene glycol tetra-acetic acid (EGTA)) or ryanodine (10(-6) M). Theophylline (1 mM) was subsequently added to one muscle bundle and, after 15 min, twitches were repeated. The twitch potentiation induced by theophylline (37 +/- 21%) was unaffected by verapamil (43 +/- 26%), or zero calcium (39 +/- 18%) and virtually unchanged when the latter was buffered with EGTA. By contrast, theophylline failed to increase twitch tension after pretreatment with ryanodine, a blocker of the calcium release by the sarcoplasmic reticulum. This decreased twitch tension in control (-5 +/- 11%) and experimental (-14 +/- 12%) bundles and prolonged half-relaxation time as a result of impaired sarcoplasmic reticulum calcium reuptake. We conclude that the inotropic effects of theophylline on twitch tension in foreshortened canine diaphragm bundles were not related to sarcoplasmic reticulum. This is consistent with an action of theophylline on the sarcoplasmic reticulum.
Aetiology and prognostic factors of patients with AIDS presenting life-threatening acute respiratory failure
Authors: Torres A , El-Ebiary M , Marrades R , Miro JM , Gatell JM , Sanchez-Nieto JM , Xaubet A , Agusti C , Rodriguez-Roisin R
Published: June 2003

Respiratory failure is a significant contributor to morbidity and mortality in patients with the acquired immune deficiency syndrome (AIDS). We performed a study to investigate the aetiology, prognostic factors, and short- and long-term outcome of AIDS patients with life-threatening respiratory failure and pulmonary infiltrates. Forty-two AIDS patients (29 of whom required mechanical ventilation), admitted to a Respiratory Intensive Care Unit (ICU) from 1985 to 1992 because of severe respiratory failure (arterial oxygen tension/fractional inspiratory oxygen (Pa,O2/FI,O2) ratio at hospital admission 19 +/- 14 kPa (mean +/- SD)) and diffuse pulmonary infiltrates, were studied for evaluation of the aetiology and outcome. Necropsy studies were performed in 14 out of 23 (61%) patients who died. Pneumocystis carinii was the most common aetiology of pulmonary infiltrates (28 patients (67%)). Overall, 19 patients survived (45%) and 23 (55%) died. A multivariate analysis of prognostic factors influencing the outcome of the whole population showed that the presence of P. carinii pneumonia and the requirement for mechanical ventilation (MV) were the major determinants of outcome for this type of patient. The median survival time after ICU discharge for P. carinii pneumonia patients was lower (49 days) when compared to that of the remaining patients (154 days). Median survival time after ICU discharge for patients needing MV (112 days) did not differ from that observed in patients not requiring artificial ventilatory support (154 days). Although the ICU survival rate in this study was reasonable, 55% for the whole population, and 36% for P. carinii pneumonia patients, the poor outcome after ICU discharge, in particular for P. carinii pneumonia patients, deserves the reassessment of ICU admission criteria for this type of AIDS population.
Nosocomial and community-acquired Legionella pneumonia: clinical comparative analysis
Authors: Pedro-Botet ML , Sabria-Leal M , Haro M , Rubio C , Gimenez G , Sopena N , Tor J
Published: June 2003

Previous reports have suggested that nosocomial and community Legionella pneumonia cases are similar. However, community and hospital characteristics, such as aquatic environment, antibiotic pressure (usage) and populations, are quite different, leading to the suspicion that Legionella infection may differ in the two settings. Univariate and multivariate analyses were performed to compare demographic data, risk factors, clinical, radiological and outcome data between 125 nosocomial and 33 community-acquired cases of Legionella pneumophila infection. Patients in the nosocomially acquired Legionella pneumonia (NALP) group were older than those in the community-acquired Legionella pneumonia (CALP) group. Univariate analysis showed that smoking habit, cough, thoracic pain, and extrapulmonary manifestations were more prevalent in the CALP group, whilst chronic lung disease and cancer were more prevalent in the NALP group. Moreover, patients in the NALP group were more likely to have received oxygen and corticosteroid therapy and also to have altered creatinine values than patients in the CALP group, whilst more patients in the latter group had altered alanine amino-transferase values. However, multivariate analysis failed to confirm most of these differences. Smoking habit and blood creatinine levels were the only variables remaining significant. In conclusion, demographic, clinical, laboratory, radiological and outcome data in nosocomial and community-acquired Legionella pneumonia are quite similar.
Parapneumonic effusions secondary to community-acquired bacterial pneumonia in human immunodeficiency virus-infected patients
Authors: Gil Suay V , Cordero PJ , Martinez E , Soler JJ , Perpina M , Greses JV , Sanchis J
Published: June 2003

The purpose of this study was to determine whether the clinical and microbiological characteristics of parapneumonic effusions in patients with community-acquired pneumonia (CAP) infected with the human immunodeficiency virus (HIV) were different from those observed in patients without HIV infection. One hundred and thirty seven patients with parapneumonic effusions were included and divided into two groups depending on whether they had HIV infection or not. The parapneumonic effusion rate was significantly higher in HIV-positive than in noninfected patients (21 vs 13%). Their clinical course was more severe, presenting a higher rate of bacteraemias (58 vs 18%). Pleural fluid in patients infected with HIV had significantly lower glucose levels than that of patients without HIV infection. Chest tube drainage was more frequent in parapneumonic effusions of patients infected with HIV than in those without HIV infection (71 vs 44%). Staphylococcus aureus was the most common microorganism found in the bacteriological samples of patients with CAP infected with HIV (53 vs 12%). We conclude that patients with community-acquired pneumonia and HIV infection have a higher rate of parapneumonic effusions and a more severe clinical course than non-HIV patients, and that Staphylococcus aureus predominates in their bacteriological samples.
Peak inspiratory flow through Turbuhaler in acute asthma
Authors: Brown PH , Ning AC , Greening AP , McLean A , Crompton GK
Published: June 2003

Efficient use of dry powder inhalers, such as Turbuhaler, is dependent on the generation of adequate inspiratory flow. It is not clear whether patients with acute asthma are able to generate adequate flow. Peak inspiratory flow (PIF) was measured through an empty Turbuhaler, and without this device, in 99 adults presenting to hospital with acute exacerbations of asthma. Where possible, patients were studied prior to nebulized bronchodilator therapy. Mean (SD) forced expiratory volume in one second (FEV1) was 1.2 (0.7) L, forced vital capacity (FVC) 2.1(1.0) L and peak expiratory flow (PEF) 199 (92) L.min-1. PIF without Turbuhaler was 152 (77) L.min-1 and correlated with PEF (r = 0.69). PIF through Turbuhaler was 60 (20) L.min-1 and weakly correlated with PEF (r = 0.35), and with PIF without Turbuhaler (r = 0.43). Two patients failed to generate the minimum inspiratory flow (30 L.min) required for efficient use of Turbuhaler; both recorded 26 L.min-1. Acute asthma is associated with considerable inspiratory, as well as expiratory airflow limitation. The relationship between inspiratory and expiratory airflow is not strong enough to predict whether patients with severe acute asthma will have difficulty using dry powder inhalers efficiently. Despite this, 98% of patients in this study generated inspiratory flow through Turbuhaler which would allow a therapeutically active amount of bronchodilator drug to be delivered to the airways.
Wheezes
Authors: Meslier N , Charbonneau G , Racineux JL
Published: June 2003

Wheezes are continuous adventitious lung sounds. The American Thoracic Society Committee on pulmonary nomenclature define wheezes as high-pitched continuous sounds with a dominant frequency of 400 Hz or more. Rhonchi are characterized as low-pitched continuous sounds with a dominant frequency of about 200 Hz or less. The large variability in the predominant frequency of wheezes is one of the difficulties encountered with automated analysis and quantification of wheezes. The large variations observed in automated wheeze characterization emphasize the need for standardization of breath sound analysis. This standardization would help determine diagnostic criteria for wheeze identification. The mechanism of wheeze production was first compared to a toy trumpet whose sound is produced by a vibrating reed. The pitch of the wheeze is dependent on the mass and elasticity of the airway walls and on the flow velocity. More recently, a model of wheeze production based on the mathematical analysis of the stability of airflow through a collapsible tube has been proposed. According to this model, wheezes are produced by the fluttering of the airways walls and fluid together, induced by a critical airflow velocity. Many circumstances are suitable for the production of continuous adventitious lung sounds. Thus, wheezes can be heard in several diseases, not only asthma. Wheezes are usual clinical signs in patients with obstructive airway diseases and particularly during acute episodes of asthma. A relationship between the degree of bronchial obstruction and the presence and characteristics of wheezes has been demonstrated in several studies. The best result is observed when the degree of bronchial obstruction is compared to the proportion of the respiratory cycle occupied by wheeze (tw/ttot). However, the relationship is too scattered to predict forced expiratory volume in one second (FEV1) from wheeze duration. There is no relationship between the intensity or the pitch of wheezes and the pulmonary function. The presence or quantification of wheezes have also been evaluated for the assessment of bronchial hyperresponsiveness. Wheeze detection cannot fully replace spirometry during bronchial provocation testing but may add some interesting information. Continuous monitoring of wheezes might be a useful tool for evaluation of nocturnal asthma and its treatment.
Objective assessment of cough
Authors: Piirila P , Sovijarvi AR
Published: June 2003

Cough is a primitive reflex typically consisting of an initiating deep inspiration, glottal closure, and an explosive expiration accompanied by a sound. The flow characteristics of cough have been shown to differ between different pulmonary diseases. Cough sounds are generated at the larynx and in the lungs. Modern analysing techniques have also been applied in cough sound studies, and differences in cough sound duration and spectra have been found in pulmonary diseases with different bronchopulmonary pathophysiology. Since the objective assessment of cough is clinically important, automatic cough detectors and counters have been constructed, e.g. to assess the efficacy of antitussive drugs. Also, ambulatory methods for assessment of cough have been reported. This review includes a brief history of cough research and present methods available for objective assessment of cough.
Occupational asthma caused by natural rubber latex
Authors: Vandenplas O
Published: June 2003

IgE-mediated sensitization in protein allergens of natural rubber latex (NRL) can induce immediate hypersensitivity reactions ranging from mild urticaria in life threatening anaphylaxis after cutaneous, mucosal or visceral exposure. Elutable allergens from NRL gloves absorb to the cornstarch powder particles, become airborne, and have the potential to cause respiratory reactions. Recent studies indicate that asthma is a frequent manifestation of NRL allergy among workers manufacturing NRL materials and among health-care providers using NRL workers. NRL-induced asthma should receive increasing attention as it can lead to permanent respiratory sequelae and occupational disability. The need for early and accurate diagnosis is outlined and the different diagnostic approaches are reviewed. Specific issues pertaining to the management of affected subjects and to the prevention of exposure to airborne NRL are discussed. Ares of future research should include: 1) further characterization of relevant NRL allergens; 2) development and validation of methods for quantitative assessment of allergen content in NRL devices and workplace environment; 3) evaluation of the natural history and risk factors of NRL-induced asthma; and 5) analysis of effectiveness and cost of preventive strategies.
Methacholine challenge does not affect bronchoalveolar fluid cell number and many indices of cell function in asthma
Authors: Kraft M , Bettinger CM , Wenzel SE , Irvin CG , Ackerman SJ , Martin RJ
Published: June 2003

Methacholine (MCh) challenge testing is often incorporated into clinical studies prior to performing bronchoscopy as a measure of bronchial hyperresponsiveness (BHR). However, the effect of methacholine on many aspects of bronchoalveolar lavage (BAL) fluid cell count and function have not been fully evaluated. Ten patients with asthma, maintained on inhaled beta 2-agonists, were studied. Each subject underwent two bronchoscopies in a random order, one preceded by methacholine challenge within 30 min of the BAL. The investigators were blinded to the regimen. Several markers of BAL fluid cell number and function were studied: cell count and differential histamine, eosinophil products, including eosinophil cationic protein and Charcot-Leyden crystal protein, macrophage production of thromboxane B2 and leukotriene B4, neutrophil lysozyme and lactoferrin, and lymphocyte typing and activation markers measured via flow cytometry. No significant differences were noted in any of these markers of cell number or function which could be ascribed to methacholine challenge. Thus, methacholine challenge does not appear to affect these markers of cell number and function. These findings indicate that a methacholine challenge can be used as a measure of bronchial hyperresponsiveness within 30 min prior to bronchoscopy without altering bronchoalveolar lavage fluid characteristics.
BOOP presenting with haemoptysis and multiple cavitary nodules
Authors: Froudarakis M , Bouros D , Loire R , Valasiadou K , Tsiftsis D , Siafakas NM
Published: June 2003

A 47 year old woman developed idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) presenting with haemoptysis and diffuse multiple cavitary nodules. The disease was histologically confirmed by open lung biopsy after other entities had been excluded. The patient responded to a course of corticosteroids. This BOOP should be added to the list of diseases with multiple cavitary nodules.