bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulocytes and their secretory products, myeloperoxidase and eosinophil cationic protein, in bronchoalveolar lavage fluids from two lung lobes in normal subjects
Authors: Schmekel B , Blom-Bulow B , Hornblad Y , Laitinen LA , Linden M , Venge P
Published: November 2022

The interlobar variability of lavage neutrophils and eosinophils was studied in twelve healthy subjects. In addition, the interlobar variation of the neutrophil cell marker myeloperoxidase (MPO) and the eosinophil cell marker eosinophil cationic protein (ECP) was assessed. Bronchial washes (BW), as defined by the first aspirated lavage aliquot, and bronchoalveolar lavage (BAL) fluids were compared. One subsegment of the right middle lobe and one subsegment of the right lower lobe were lavaged in the same session. Interlobar consistency of neutrophil and eosinophil cell recoveries was observed but, in contrast, the levels of MPO or ECP did not correlate in lavage fluids aspirated from the two lobes. These results suggest that BAL cell content from a single lobe of the lung in healthy subjects does reflect the cell populations throughout the airways, while the levels of soluble proteins may differ between the lobes. Such a variation questions the correlation between cells and their secretory products or the correlation between levels of solutes in lavage fluid and in the underlying tissue. Further methodological studies appear warranted to elucidate whether cell and solute recoveries accurately reflect the underlying pathology.
Effect of salbutamol on dry air- and acetylcholine-induced bronchoconstriction in the canine lung periphery
Authors: Teeter JG , Freed AN
Published: November 2022

We examined the effect of salbutamol on dry airflow-induced bronchoconstriction (AIB) and acetylcholine-induced bronchoconstriction (Ach-IB) in the canine lung periphery using a wedged bronchoscope technique. Collateral system resistance (Rcs) and airway wall temperature (Taw) were monitored in a peripheral lung segment before, during and after airflow challenge. Rcs before and after aerosolized acetylcholine was recorded in a contralateral lung segment. Intravenous salbutamol (2.5 micrograms.kg-1) significantly attenuated the peak fall in Taw during airflow challenge and the peak rise in Rcs following challenge. Intravenous salbutamol attenuated Ach-IB to a similar degree. Significant systemic effects were recorded following i.v. salbutamol. In contrast, aerosolized salbutamol (50 micrograms) minimally decreased the fall in Taw during airflow challenge, while virtually eliminating AIB. The same dose of aerosolized salbutamol only partially attenuated Ach-IB. Aerosolized salbutamol did not affect mean arterial pressure or heart rate. Intravenous salbutamol may in part inhibit AIB by increasing pulmonary blood flow, secondary to its systemic circulatory effects, and decrease heat and water loss during airflow challenge. In contrast, aerosolized salbutamol abolished AIB, while only minimally effecting airway cooling. These data suggest that AIB is a result of mediator release and/or smooth muscle contraction.
Influence of water content of inspired air during and after exercise on induced bronchoconstriction
Authors: Boulet LP , Turcotte H
Published: November 2022

This study looked at the influence of inspired air water content on exercise-induced bronchospasm (EIB). On separate days, 12 mild asthmatics (4M, 8F), aged 18-39 yrs (mean: 27 yrs), performed four six minute steady-state exercises on ergometer at 80% of their maximum workload. Exercises were randomized to the following inspired air conditions: dry air (0% relative humidity (RH] during exercise followed by dry (DD) or humid air (100% RH) (DH) after exercise, humid air during exercise followed by dry (HD) or humid air (HH). Room temperature was kept constant (22 +/- 1 degree C) at all visits. Forced expiratory volume in one second (FEV1) was measured before and every 5 min for 25 min after exercise. Ventilation (VE) was not significantly different whether the exercise was done under dry or humid air. There was a residual bronchodilatation at the end of exercises performed in humid air, while at this time FEV1 was already lower than baseline when exercise was done in dry air conditions. The maximal fall in FEV1(%) following exercise was significantly greater after those performed in dry air: DD (29 +/- 5.6%) and DH (30 +/- 5.8%) than in humid air: HD (12 +/- 4.9%) and HH (20 +/- 4.9%) (p less than 0.05). The time-course of recovery from bronchoconstriction was significantly improved when inhaling dry air after exercise. However, the difference found in the maximal % fall in FEV1 after exercise when recovery was in dry compared to humid air did not achieve statistical significance. In conclusion, EIB is influenced by the changes in water content during and after exercise. Bronchoconstriction following exercise is minimal if exercise is done in humid air and recovery in dry air, and maximal if the exercise is performed in dry air and recovery in humid air.
Domiciliary nocturnal nasal intermittent positive pressure ventilation in COPD: mechanisms underlying changes in arterial blood gas tensions
Authors: Elliott MW , Mulvey DA , Moxham J , Green M , Branthwaite MA
Published: November 2022

The improvement in arterial blood gas tensions following assisted ventilation in chronic obstructive pulmonary disease (COPD) has usually been attributed to the relief of incipient or established respiratory muscle fatigue. The contribution of changes in the load placed upon and the drive to the respiratory muscle pump have not been evaluated. We have investigated the contribution of changes in respiratory muscle strength, the ventilatory response to CO2 and ventilatory function to changes in arterial blood gas tensions in eight patients with severe COPD completing six months domiciliary nasal intermittent positive pressure ventilation. Six patients showed a reduction and two an increase in arterial carbon dioxide tension (PaCO2), median (range) for eight patients, -0.9 kPa (-1.5 to +0.4) (p less than 0.05) and seven showed an improvement in arterial oxygen tension (PaO2), +0.7 kPa (-0.4 to +1.7) (p less than 0.05) during daytime spontaneous breathing. The reduction in PaCO2 was not related to increased inspiratory muscle strength but was correlated with a decrease in gas trapping (Spearman rank correlation coefficient (r(S)) 0.85, p less than 0.05) and in the residual volume (r(s) 0.78, p less than 0.05), suggesting reduced small airway obstruction and, therefore, a reduction in load. The change in PaCO2 also correlated with the increase in ventilation at an end-tidal CO2 of 8 kPa during rebreathing (r(s) -0.76, p less than 0.05) suggesting improved chemosensitivity to CO2. Our data do not support the hypothesis that improvements were due to the relief of muscle fatigue. We suggest that the contribution of changes in load and central drive warrant further investigation.
Increased coagulation activity of the pleura after tube drainage and quinacrine instillation in malignant pleural effusion
Authors: Agrenius V , Chmielewska J , Widstrom O , Blomback M
Published: November 2022

Chronic malignant pleural effusions are usually treated with an intrapleurally administered irritant that creates an inflammatory reaction. The induced inflammation results in fibrin deposition and termination of fluid exudation. In the present study several factors in the coagulation system in the pleural fluid were followed during treatment with tube drainage and quinacrine instillation into the pleural space. In the chronic exudative phase before treatment, both thrombin activity and fibrinopeptide A (FPA), were present at low levels. During treatment the levels increased markedly. Beta-thromboglobulin, a platelet marker, showed a similar pattern. Prothrombin, antithrombin III, prekallikrein and kallikrein inhibiting activity showed no such variations in activity. The high thrombin activity and FPA level induced by treatment reflect an active process of fibrin formation which seems to play an important role in arresting chronic pleural exudation.
A study with cumulative doses of formoterol and salbutamol in children with asthma
Authors: Foucard T , Lonnerholm G
Published: November 2022

In a double-blind, cross-over study, 9 children (7-13 yrs old) with stable, moderate asthma inhaled formoterol (6, 18 and 54 micrograms) and salbutamol (100, 300 and 900 micrograms) at hourly intervals, in order to compare the peak effect of cumulative doses of the two drugs. One hour after the last dose, 1 mg salbutamol was inhaled to ensure that maximum bronchodilatation was obtained. The forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), forced vital capacity (FVC), pulse rate, blood pressure and tremor were measured regularly after each dose and the PEFR 5, 7, 9 and 20 h after the last dose. The first dose of each drug improved the FEV1, PEFR and FVC substantially while the following doses only gave minor improvement. The final addition of 1 mg salbutamol produced no further improvement. No statistically significant difference in bronchodilating effect was seen between the two drugs at any point in time. Side-effects were minimal. Our data indicate that doses of 6-24 micrograms formoterol can be recommended for school children. For most patients with mild to moderate bronchial asthma higher doses will not add much to the bronchodilating effect.
Influence of lung volume on histamine-induced bronchoconstriction in guinea-pigs
Authors: Lorino AM , Benichou M , Macquin-Mavier I , Franco-Montoya ML , Lorino H , Harf A
Published: November 2022

The influence of lung volume on bronchopulmonary reactivity was investigated in 4 groups of 14 anaesthetized paralysed mechanically ventilated guinea-pigs: animals of group 1 served as control; in animals of group 2, the parasympathetic nervous system was blockaded with atropine; animals of group 3 were submitted to a bilateral cervical vagotomy; animals of group 4 were both vagotomized and pretreated with atropine. In each group, the animals were randomly divided into 2 subgroups: one was ventilated at zero end-expiratory pressure (ZEEP), the other with 0.2 kPa positive end-expiratory pressure (PEEP) resulting in a mean increase in lung volume of about 1 ml. Bronchopulmonary response to infused histamine was assessed by the respiratory conductance and compliance values measured during bronchoconstriction (respectively HGrs and HCrs). In the control group, animals exposed to PEEP were found significantly less reactive than those ventilated at ZEEP. In groups 2, 3 and 4, this difference was significantly reduced for HGrs and even abolished for HCrs. These results demonstrate that the effect of lung volume on moderate histamine-induced bronchoconstriction in guinea-pigs is not purely mechanical, but is partly vagally mediated. They also suggest that this vagally mediated inhibitory influence results from involvement of central reflexes evoked by stretch receptor stimulation.
Collateral ventilation by diffusion across the alveolar walls and the exchange of inert gases in the lung
Authors: Luijendijk SC , de Vries WR , Zwart A
Published: November 2022

The underlying hypothesis of this study is that collateral ventilation by diffusion of occluded air spaces in the lungs of patients with chronic obstructive pulmonary disease (COPD) may play a substantial role in the pulmonary gas exchange of these patients. Using a related lung model we have simulated: a) the multiple-breath washout of helium (He) and sulphur hexafluoride (SF6) from the alveolar space, and b) the washout of inert tracer gases with different blood-gas partition coefficients, range 0.01-330, from mixed venous blood. These computations were carried out for different values of the collateral diffusion capacity (CDC). Next, the results obtained at each individual value of CDC were used to compute the breath number (NCR) at the crossing-over of the He-SF6 washout curves and the inert gas shunt fraction QS/QC. NCR and QS/QC range up to about 100 and 0.04, respectively, when CDCSF6 ranges down to about 0.1 ml.min-1.mmHg-1. These ranges for NCR and QS/QC, and the typical finding of relatively large values for NCR in combination with small values for QS/QC, are also reported in the literature for patients with COPD. These agreements thus support our hypothesis. In line with the small values for QS/QC, our results further indicate that even large, well-perfused, occluded air spaces in the lung will hardly affect the recovered ventilation/perfusion distribution obtained from inert gas data when CDCSF6 exceeds 0.1 ml.min-1.mmHg-1.
Mediator concentrations in bronchoalveolar lavage fluid of patients with mild asymptomatic bronchial asthma
Authors: Crea AE , Nakhosteen JA , Lee TH
Published: November 2022

Bronchoalveolar lavage (BAL) was performed on 11 atopic patients with mild asymptomatic bronchial asthma and 11 healthy nonasthmatic volunteers. All asthmatic subjects had evidence of bronchial hyperresponsiveness to inhaled carbachol. The concentrations of leukotriene (LT) C4, LTD4, LTE4, LTB4, prostaglandin D2 (PGD2), platelet-activating factor (PAF) and histamine in BAL fluid measured. The leukotrienes were measured by radioimmunoassay following reverse phase high performance liquid chromatography. PGD2 concentrations were determined by radio immunoassay after Amprep C2 extraction. PAF was quantitated by means of in vitro aggregation of rabbit platelets and histamine content was measured using a single isotope radio-enzymatic assay. There was an increase in the levels of PGD2 and a decrease in the concentration of LTB4 in asthmatic lavage samples. There were no significant differences in the lavage concentrations of LTC4/D4/E4 and histamine between the two groups of individuals. PAF was undetectable.
A trial of ranitidine in asthmatic children and adolescents with or without pathological gastro-oesophageal reflux
Authors: Gustafsson PM , Kjellman NI , Tibbling L
Published: November 2022

In order to study the importance of gastro-oesophageal reflux (GOR) as a trigger of asthma the effect of inhibition of gastric acid secretion on asthma was assessed in a double-blind, cross-over, placebo-controlled trial over four weeks in 37 children and adolescents (mean age 14 yrs) with bronchial asthma. Ranitidine 300 mg, (150 mg if B.W. was less than 40 kg) was given as a single evening dose during four weeks. In previous investigations 18 of the 37 patients had been shown to have pathological GOR by 24 h pH monitoring in the oesophagus. The remaining 19 patients with normal GOR served as controls for possible effects of ranitidine on asthma, not related to reduction of GOR. A modest (30%) but statistically significant reduction of nocturnal asthma symptoms was produced by ranitidine in the patients with pathological GOR when compared to those with normal GOR. There was a significant correlation between the improvement in asthma symptoms and the degree of acid reflux. Side-effects of ranitidine were negligible. Acid reflux appears to be only a weak stimulus for bronchoconstriction in children and adolescents with bronchial asthma and pathological GOR. Further confirmative trials with more potent inhibitors of gastric acid secretion are, however, warranted.
Sensitivity of the cough reflex in patients with chronic cough
Authors: Choudry NB , Fuller RW
Published: November 2022

Cough may occur in association with excess bronchial secretions and may, therefore, be productive. However, in a proportion of patients the cough is non-productive and a possible association with an enhanced response of the cough reflex has been postulated. Using the irritant capsaicin, the sensitivity of the cough reflex was measured in 363 individuals. A questionnaire was used to divide subjects into three groups: Group A) non-coughing controls; Group B) subjects with non-productive cough; and Group C) subjects with productive cough. The group means (+/- 99% confidence interval (CI)) of the log capsaicin concentration causing two or more coughs (C2) for groups A, B, C were 0.98 (+/- 0.08), 0.64 (+/- 0.09) and 1.04 (+/- 0.23), respectively. The log capsaicin concentration causing five or more coughs (C5) for groups A, B, C were 1.78 (+/- 0.1), 1.16 (+/- 0.12) and 1.54 (+/- 0.25), respectively. Group B was significantly more sensitive to inhaled capsaicin than the other groups (p less than 0.01). No significant difference was observed between groups A and C. Some differences were found when subgroups were examined within groups B and C. In group B, patients with post-nasal drip were found to have a normal sensitivity of the cough reflex and were, therefore, different from the remainder of patients with non-productive cough. In group C, patients with bronchiectasis and current infection showed an increase in the sensitivity of their cough reflex. It is concluded that cough can occur in association with either excess mucus production leading to productive cough or an increase in the sensitivity of the cough reflex, possibly leading to non-productive cough.
The relative contributions of histamine and prostanoids to bronchoconstriction provoked by isocapnic hyperventilation in asthma
Authors: Finnerty JP , Harvey A , Holgate ST
Published: November 2022

It has been proposed that exercise provokes bronchoconstriction in asthma by inducing mast cell degranulation, and that this occurs secondary to the hyperpnoea of exercise causing hypertonicity of the airway lining fluid. We investigated the contribution of the mast cell products, histamine and prostaglandins, to the bronchoconstriction induced by isocapnic hyperventilation (ISH) using single doses of terfenadine, a specific histamine H1-receptor antagonist, and flurbiprofen, a potent cyclooxygenase inhibitor. We also investigated the effect of flurbioprofen in single dose on bronchial histamine reactivity. Eleven asthmatics took part in a two phase, double-blind, randomized study. In phase 1, subjects attended on three occasions and received either terfenadine 180 mg, flurbiprofen 150 mg, or placebo, prior to 6 min of ISH. The mean maximum percentage fall in forced expiratory volume in one second (FEV1) induced by ISH was 31.5(+/- 3.2)% following placebo, 29.7(+/- 4.4)% following flurbiprofen (NS), and reduced to 16.6(+/- 3.7)% following terfenadine (p less than 0.01). In phase 2, subjects received bronchial challenge with histamine following either flurbiprofen 150 mg or placebo. No significant change in bronchial reactivity following flurbiprofen was seen. We conclude that as administered in this study, flurbiprofen has no effect on baseline bronchial reactivity to histamine. The inhibitory effect of terfenadine indicates that histamine, probably from airway mast cells, makes an important contribution to bronchoconstriction induced by isocapnic hyperventilation, whereas prostaglandin release has no significant role.
The effect of phosphoramidon and epithelium removal on toluene diisocyanate-induced contractions in guinea-pig bronchi
Authors: Mapp CE , Boniotti A , Papi A , Chitano P , Saetta M , Di Stefano A , Ciaccia A , Fabbri LM
Published: November 2022

To evaluate the role of airway neutral endopeptidase 24.11 (NEP) and epithelium removal in the contraction of airway smooth muscle in response to toluene diisocyanate (TDI), we studied the effects of the NEP inhibitor, phosphoramidon, on TDI-induced contractions of guinea-pig bronchial rings with intact epithelium and without epithelium. In preparations with intact epithelium, phosphoramidon (10 microM) potentiated the contractile response to TDI (0.3 mM) (mean +/- SEM, 23.7 +/- 2.5% versus 67.9 +/- 10.3%, p less than 0.01). Phosphoramidon also increased TDI-induced contractions in tissues without epithelium (36.9 +/- 4.9% versus 52.5 +/- 7.1%, p less than 0.05). Removal of the epithelium increased the contractile response to TDI (23.7 +/- 2.5% versus 36.9 +/- 4.9%, p less than 0.05). These results demonstrate the response to TDI is increased in epithelium-free compared to intact bronchi and that NEP 24.11 modulates the effects of endogenously released tachykinins by TDI at all of the sites where NEP is found in the airways.
Right ventricular diastolic function in chronic obstructive lung disease
Authors: Marangoni S , Scalvini S , Schena M , Vitacca M , Quadri A , Levi G
Published: November 2022

Early detection of diastolic dysfunction in chronic obstructive lung disease (COLD) patients could have great prognostic value. Echocardiography has been shown to be a useful technique in studying left ventricular diastolic function. A noninvasive method of studying right ventricular diastolic function has not yet been reported. Pulsed Doppler echocardiography was used to assess right ventricular diastolic function in three groups of subjects: Group I: 35 COLD patients with pulmonary hypertension; Group II: 32 COLD patients without pulmonary hypertension; and Group III: 18 control subjects. Ratios between peak atrial filling velocity (A) and peak early filling velocity (E) (A/E), deceleration half times of the right ventricular rapid filling wave (DHT), and the interval between pulmonary valve closure and tricuspid valve opening (isovolumic relaxation times) (Pc-To) were significantly different in Group I in comparison to Groups II and III. Sensitivity of A/E ratio and Pc-To were 82 and 77%, respectively, and specificity 90 and 72%, respectively; positive predictive values were 90 and 75%, respectively, and negative predictive value 82 and 74% respectively. The multiple correlation coefficient between A/E, acceleration time (ACT), DHT, Pc-To and mean pulmonary artery pressure was 0.75 for Groups I and II together. In conclusion 2D echo-Doppler proved to be useful in evaluating right ventricular diastolic function in all hypertensive COLD patients, revealing a high correlation between diastolic parameters and mean pulmonary artery pressure in both normotensive and hypertensive COLD patients.
Sensitivity to sensitins and tuberculin in Swedish children. IV. The influence of BCG-vaccination
Authors: Larsson LO , Magnusson M , Skoogh BE , Lind A
Published: November 2022

BCG-vaccinated schoolchildren, 8-9 yrs of age, were simultaneously tested on separate arms with tuberculin and a sensitin. Using the 6 mm cut-off they reacted in 49% to two tuberculin units purified protein derivative (PPD RT23), in 67% to 0.1 micrograms Mycobacterium avium sensitin RS10, and in 58% to 0.1 micrograms M. scrofulaceum sensitin RS95. The corresponding figures for non-BCG-vaccinated schoolchildren of the same age tested at the same time were 3, 25 and 32%, respectively. The results indicate a stimulating influence of BCG-vaccination on tuberculin and sensitin reactivity. Since the sensitin reactions were the larger ones, these reactions were not only due to the vaccination. The BCG-vaccinated schoolchildren seem to have acquired infections by atypical mycobacteria despite vaccination.
Inter-machine variability in the stability of continuous positive airway pressure
Authors: Jackson M , King MA , Shneerson JM
Published: November 2022

Two studies were performed to investigate the differences in pressure stability performance of the continuous positive airway pressure (CPAP) machines used by our patients. The variations of mask pressures during each respiratory cycle were measured during overnight studies of two groups of patients with obstructive sleep apnoea, who were using either a Sleep-Easy III CPAP machine or a Si-Plan CPAP unit. The patients were well-matched for age, weight and neck circumference. The group using the Si-Plan unit had more constant mask pressures and were using lower CPAP pressures (mean 10.6 cmH2O) than those using the Sleep-Easy III machine (mean 13.8 cmH2O) (p less than 0.02). The pressure stability performance of five CPAP machines used by our patients was also compared using standardized simulated patient breaths produced by a negative pressure cuirass pump. There were large differences between the machines in ability to maintain a constant pressure. Using a tidal volume of 0.5 l and peak flow rates of between 20-40 l.min-1 the pressure variation ranged from 0-67% of the minimum inspiratory pressure. The maintenance of a constant pressure during inspiration and expiration lowers the mean pressure required to eliminate obstructive sleep apnoeas and reduces the likelihood of pressure related side-effects.
Alveolar haemorrhage with pleural effusion as a manifestation of epithelioid haemangioendothelioma
Authors: Struhar D , Sorkin P , Greif J , Marmor S , Geller E
Published: November 2022

A 22 year old male was admitted with haemoptysis. A chest X-ray showed bilateral confluent alveolar infiltrates. Bronchoscopy revealed blood oozing from all bronchopulmonary segments. Open lung biopsy disclosed bilateral effusions and large necrotizing nodules with pleural adhesions. Histological examination showed tumour cells, which were negative to epithelial and embryogenic markers but positive to factor VIII. This confirmed the diagnosis of an epithelioid haemangioendothelioma. This rare tumour, usually has an indolent course, whereas in our case it was complicated by alveolar and intrapleural bleeding.
Increased oxidized methionine residues in BAL fluid proteins in acute or chronic bronchitis
Authors: Maier KL , Leuschel L , Costabel U
Published: November 2022

Phagocytic cells such as alveolar macrophages (AM) or polymorphonuclear neutrophils (PMN) in the bronchoalveolar tract are a potential source of the oxygen-derived free radicals which are presumed to be involved in lung tissue damage. Previous results have shown that the methionine sulphoxide (MET(O)) content of bronchoalveolar lavage fluid (BALF) protein is a reliable parameter to indicate oxidative processes in idiopathic pulmonary fibrosis (IPF). We measured the molar ratio between MET(O) and methionine (MET) in the BALF protein from healthy nonsmokers (control group), healthy smokers and patients with acute or chronic bronchitis (AB or CB). The MET(O)/MET ratio of the nonsmoking group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). Healthy smokers (n = 8) had similar values (0.042 +/- 0.008), even though they had strongly increased AM counts in BALF. Patients with AB (n = 12) showed an increased MET(O)/MET ratio (0.191 +/- 0.031) and had high PMN but normal AM counts in BALF. Patients with CB (n = 13) showed an increase in the MET(O)/MET ratio (0.086 +/- 0.010) and moderately increased PMN and markedly increased AM counts. Taking all results together, the MET(O)/MET ratio correlated positively with the relative PMN number (r = 0.70; p less than 0.0002) and inversely with the relative AM number (r = 0.67; p less than 0.0002). In the group with CB, the MET(O)/MET ratio correlated inversely with forced expiratory volume in one second (FEV1) % pred. (r = -0.77) and FEV1/inspiratory vital capacity (IVC) % pred. (r = -0.89).(ABSTRACT TRUNCATED AT 250 WORDS)
Combined chemotherapy including rifabutin for rifampicin and isoniazid resistant pulmonary tuberculosis. G.E.T.I.M. (Group for the Study and Treatment of Resistant Mycobacterial Infection)
Authors: Pretet S , Lebeaut A , Parrot R , Truffot C , Grosset J , Dinh-Xuan AT
Published: November 2022

A prospective multicentre open study has been conducted in France in order to assess the efficacy and tolerability of an antimycobacterial regimen including rifabutin in the treatment of patients with pulmonary tuberculosis due to rifampicin and isoniazid resistant bacilli. Patients were treated with daily rifabutin (450-600 mg), associated with companion drugs to which the organisms remained susceptible; in most cases the regimen included a fluoroquinolone. The duration of treatment was initially scheduled for a minimum period of 12 months after sputum culture conversion. Thirty nine patients were enrolled, 23 of whom were treated for at least 12 months. Culture conversion was obtained at the end of the twelfth month in 14 out of 23 patients. Twenty one out of 39 patients experienced adverse events. These were, however, serious enough to discontinue treatment in only four patients. These results suggest that an antimycobacterial combination including rifabutin might contribute to the treatment of multi-resistant pulmonary tuberculosis.
In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans
Authors: Manso G , Baker AJ , Taylor IK , Fuller RW
Published: November 2022

Glucocorticosteroids are used as anti-inflammatory agents in a range of diseases, however, their mechanism of action is unknown. Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung.
Mucus clearance with three chest physiotherapy regimes in cystic fibrosis: a comparison between postural drainage, PEP and physical exercise
Authors: Lannefors L , Wollmer P
Published: November 2022

The effects of three different regimes of chest physiotherapy were compared in this cross-over study. Mucus clearance was monitored in nine clinically stable cystic fibrosis (CF) patients. The patients performed: 1) postural drainage with thoracic expansion exercises + forced expiration technique (FET) in the left decubitus position; 2) positive expiratory pressure (PEP)-mask breathing + FET; and 3) physical exercise on a bicycle ergometer + FET. All treatments had the same duration and FET was standardized. Mucus clearance was assessed using a technique based on measurement of the elimination of inhaled radiolabelled particles. Mean clearance of tracer from the right lung by postural drainage, PEP and physical exercise was 18% (range 10-29%), 20% (12-43%), 16% (8-25%), respectively, and from the left lung 20% (8-42%), 15% (5-23%) and 13% (5-17%), respectively. The differences were not statistically significant. Surprisingly, postural drainage (PD) was the most effective technique in the left, dependent lung in 7 of the 9 patients.
Adherence to entry criteria and one year experience of long-term oxygen therapy in Poland
Authors: Gorecka D , Sliwinski P , Zielinski J
Published: November 2022

The adherence to entry criteria and results of one year long-term oxygen therapy (LTOT) in Poland were analysed. Four hundred and seven patients with advanced respiratory failure due to chronic lung diseases qualified for LTOT were observed for one year in 12 regional LTOT centres. There were 315 patients with chronic obstructive pulmonary disease (COPD) and 92 with other chronic lung diseases. In 270 patients the prescription of oxygen was based on the single criterion of stable arterial oxygen tension (PaO2) less than or equal to 55 mmHg (7.3 kPa); and in the remaining 137 with less severe stable hypoxaemia (PaO2 56-65 mmHg) (7.4-8.6 kPa), on concomitant signs of cor pulmonale and/or of tissue hypoxia. Of 407 patients who started LTOT, 95 (23%) died during the first year of treatment. The mortality rate was 21% for COPD patients and 33% for patients with other lung diseases. After one year of LTOT 312 patients survived: 250 COPD patients and 62 with other lung diseases. Of these, 19 COPD patients (8%) and 9 with other chronic lung disease (15%) who had PaO2 less than or equal to 55 mmHg (7.3 kPa) when oxygen was prescribed, presented with PaO2 greater than 55 mmHg (7.3 kPa). From the 137 patients (106 with COPD and 31 with other lung diseases) who qualified with less severe hypoxaemia, 10 COPD patients (10%) and 5 (16%) with other lung disease had PaO2 greater than 65 mmHg (8.6 kPa).(ABSTRACT TRUNCATED AT 250 WORDS)
Update on an exposure system for particles in the diagnosis of occupational asthma
Authors: Cloutier Y , Malo JL
Published: November 2022

We have previously designed a system for exposure to particles and described the preliminary results in 20 subjects exposed to occupational sensitizers in powder form (Cloutier Y, et al. - Eur Respir J, 1989; 2: 769). Modifications have been made to the particles generator, exposure chamber and sampling ports. Furthermore, in order to improve the stability of concentrations in the exposure chamber and to make the system easy to operate by a technician, it has been completely automated using closed-loop feedback regulated by a computer program.
Factors associated with bronchial hyperresponsiveness in Australian adults and children
Authors: Peat JK , Salome CM , Woolcock AJ
Published: November 2022

To accurately assess putative risk factors for bronchial hyperresponsiveness (BHR), we have used multivariate models to analyse data from 4,366 children living in four regions and from 878 adults. A standard protocol was used to measure bronchial responsiveness to histamine. The prevalence of BHR was high at 7-9 yrs (16-18%), decreased significantly at 11-14 yrs (7-8%), and then increased in adults (12-14%). Atopy was the most important risk factor for BHR at all ages. In children, parental asthma, early respiratory illness and being born in Australia also had a significant influence, and eating fish more than once a week had a protective effect. No effect of parental smoking, gender or race was found. In adults, BHR was associated with being female and with smoking history. It appears that many factors have a significant influence on the presence of BHR, with environmental factors, particularly atopy, birthplace and diet, being the most important.
Dose duration of nebulized nedocromil sodium in exercise-induced asthma
Authors: Albazzaz MK , Neale MG , Patel KR
Published: November 2022

The dose-duration effect of nebulized nedocromil sodium was studied in ten patients with exercise-induced asthma (7 males mean (SEM) age 30.1 (3.5) yrs and predicted forced expiratory volume in one second (FEV1) 102%). All of these patients showed > 40% protection of their exercise asthma with 4 mg of nedocromil sodium delivered via metered dose inhaler. Three concentrations of nedocromil sodium (0.5, 2.5 and 10 mg.ml-1) and placebo were administered in double-blind, randomized manner. One ml of each solution was nebulized via a Wright nebulizer. Effects were assessed from the mean maximal percentage fall in FEV1 after 6-8 min treadmill exercise at 15, 135 and 255 min following each treatment and expressed as percentage protection. The mean baseline FEV1 values before and after treatments were comparable on four days of testing. Nedocromil sodium inhibited exercise-induced fall in FEV1 at all concentrations (p < 0.001) and the inhibitory effect was still present at 255 min. No differences were observed between active treatments.
Platelet-activating factor-induced contraction of human isolated bronchus
Authors: Johnson PR , Black JL , Armour CL
Published: November 2022

In recent years, platelet-activating factor (PAF) has been strongly implicated as a mediator involved in asthma. In non-asthmatic subjects, aerosolized PAF has been shown to cause bronchoconstriction. The mechanism of this in vivo effect is unknown. We have previously shown that PAF causes a contraction of human isolated bronchus that varies in magnitude between patients, and within tissues from the same patient. To examine the possibility that this variability in contraction was secondary to PAF-induced release of mediators from inflammatory or epithelial cells within the tissue, we examined the relationship between contractile responses to PAF and the presence of inflammatory or epithelial cells. We studied eight tissues from five patients. Of the eight tissues, four contracted, whilst four failed to contract, to PAF (7 x 10(-7) M). After the contractile response to PAF had been assessed by observing changes in isometric tone in vitro, bronchial rings were examined histologically to enable the quantification of inflammatory cell numbers and intact epithelium. No significant correlation was observed between the magnitude of contractions and numbers of eosinophils, neutrophils, lymphocytes, plasma cells, total cells or percentage intact epithelium. We conclude that it is unlikely that the variability in response to PAF in human isolated airways is related to the variability in inflammatory cell numbers or to the presence of epithelium. Thus, the contraction induced by PAF is probably not mediated via the release of a secondary mediator from the particular cells examined in this study.
Bronchodilatory effect of inhaled zardaverine, a phosphodiesterase III and IV inhibitor, in patients with asthma
Authors: Brunnee T , Engelstatter R , Steinijans VW , Kunkel G
Published: November 2022

Zardaverine is a newly developed selective phosphodiesterase III and IV inhibitor. This study investigates the bronchodilatory properties of zardaverine, administered by inhalation. Twelve patients with reversible bronchial obstruction (increase in forced expiratory volume in one second (change FEV1 % predicted) at least 15% after 200 micrograms salbutamol, median age 31 yrs, range 21-54 years) entered the double-blind, crossover study. Four puffs of either zardaverine (total dose 6 mg) or placebo were inhaled at 15 min intervals. Pulmonary function (specific airway conductance (sGaw) and FEV1 was measured by body plethysmography at regular intervals (5 and 12 min after each puff and, in addition, 30, 60, 120, 180 and 240 min after the last puff). Compared to placebo, sGaw and FEV1 increased significantly during the first hour of repeated inhalations, but not during the entire observation period of almost 5 h. The maximum mean difference between zardaverine and placebo for FEV1 was 0.3 l or 12% and occurred approximately 1 h after inhalation of the first puff. In seven patients FEV1 increased by > 15%. The duration of action varied considerably between patients. Three patients complained of side-effects (headache, drowsiness, vertigo, nausea), and one of these dropped out of the study due to vomiting. We conclude that inhalational administration of zardaverine has a modest and short-lasting bronchodilating activity.
Perceived effect on shortness of breath of an acute inhalation of saline or terbutaline: variability and sensitivity of a visual analogue scale in patients with asthma or COPD
Authors: Noseda A , Schmerber J , Prigogine T , Yernault JC
Published: November 2022

The purpose of the study was to validate a bipolar visual analogue scale (VAS) to assess the perceived effect on shortness of breath of an acute inhalation and to search for differences in perception between asthmatics and subjects with chronic obstructive pulmonary disease (COPD). Thirty two subjects with airway obstruction and a diagnosis of either asthma (n = 16) or COPD (n = 16) received three consecutive inhalations of isotonic saline, followed by two inhalations of 400 micrograms terbutaline. Saline was perceived by asthmatics as a slight improvement: VAS (median, 95% confidence interval) 9%, 0-18% of line length. COPD subjects could be separated into two subgroups: "high perceivers" (n = 8, VAS 43%, 33-53%) and "low perceivers" (n = 8, VAS 5%, 3-7%). The median intrasubject coefficient of variation of the three post-saline VAS ratings was 19.4% (asthma), 12.5% (COPD high perceivers), and 14.5% (COPD low perceivers). After terbutaline, asthmatics had, by selection, a larger increase in forced expiratory volume in one second (FEV1) than COPD subjects. However, for other indices (expiratory specific resistance, inspiratory vital capacity and maximal inspiratory flow at 50% forced vital capacity) the changes were smaller in COPD low perceivers than in both asthmatics and COPD high perceivers. The parallel improvement in VAS was 24%, 20-39% (asthma), 15%, 6-25% (COPD high perceivers) and 1%, -1-8% (COPD low perceivers). The most sensitive index was FEV1 in asthmatics, vital capacity in COPD subjects, VAS being among the most sensitive indices in the former, but among the least sensitive in the latter. We conclude that the sensitivity of this VAS to bronchodilation is better in asthmatics than in COPD subjects. The latter can however be separated into subgroups with high and low level of perception.
Sequential treatment with low dose almitrine bismesylate in hypoxaemic chronic obstructive airways disease
Authors: Bardsley PA , Howard P , Tang O , Empey D , Harrison B , Peake MD , O'Reilly J , Riordan JF , Wilkinson J , Arnaud F , et al.
Published: November 2022

Daily dose schedules of 100-200 mg of almitrine bismesylate improve arterial blood gases in patients with hypoxaemic chronic obstructive airways disease (COPD) but dose related side effects are evident. In the present study, daily doses approximately half of those previously used were employed in a randomised double blind manner in 85 patients (age 35-79 years) with hypoxaemic COPD. After a one month period to check stability of arterial blood gases, patients were allocated to almitrine (A) or placebo (P) using an unequal code (60% A, 40% P). Tablets, 50-100 mg daily were stopped for one month after 3, 6 and 9 months to counteract drug accumulation. 50 patients in group A and 35 in group P were comparable on entry; mean age 65 (SD = 8) yrs., Pao2 7.8 (0.7) kPa (58.3 (5.0) mmHg), PaCO2 5.8 (0.8) kPa (43.2 (6.0) mmHg), forced expiratory volume in one second--FEV1 0.89 (0.25) l and 6 minute walking distance 296 (97) metres. The improvement in baseline PaO2 values was the same 0.8-1.3 kPa (6-9.8 mmHg) as with previous higher dose therapy. Approximately one third of patients did not respond, defined as PaO2 elevation > 0.67 kPa (5 mmHg). The sequential dosing scheme stabilised blood levels of almitrine within the therapeutic range of 280-300 ng.ml-1. After withdrawal of therapy arterial blood gases and spirometry reverted to pre-treatment levels, suggesting no permanent reversal of pathophysiology. Dose related side effects of breathlessness, indigestion and peripheral neuropathy were not observed. Nerve conduction studies revealed no difference in peripheral nerve dysfunction in hypoxaemic COPD between active and placebo therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Easy bruising as a side-effect of inhaled corticosteroids
Authors: Mak VH , Melchor R , Spiro SG
Published: November 2022

We wished to determine the prevalence of easy bruising in patients taking inhaled corticosteroids (ICS) compared with those who do not. Differences in age, dosage and duration of use of ICS between patients who bruised and those who did not were also investigated. Confidential questionnaire surveys were conducted over a 6 month study period amongst patients attending a respiratory out-patient clinic and taking regular ICS, and a control group of patients attending non-respiratory clinics and not taking any form of corticosteroids. Patients with bleeding disorders or taking oral steroids, non-steroidal anti-inflammatory drugs or anticoagulants were excluded from the study. Questionnaires from 202 respiratory patients using ICS (group A) were compared with 204 non-ICS patients (Group B) of similar age and sex distribution. Significantly more patients in Group A reported easy bruising than in group B (47 vs 22%, relative risk 2.18, 95% confidence interval (95% CI) 1.62-2.94), and it was the commonest reported symptom. In Group A, the patients that reported easy bruising tended to be older (61 vs 52 yrs), on higher daily dosages (1,388 vs 1,067 micrograms) and had been taking inhaled corticosteroids for longer (55 vs 43 months) than non-bruisers. Overall, females reported easy bruising more frequently than males in both groups. However, comparing Group A with Group B, males taking ICS had a higher relative risk for bruising than females (males, relative risk 5.80, 95% CI 2.38-14.13; females, relative risk 1.80, 95% CI 1.32-2.44).(ABSTRACT TRUNCATED AT 250 WORDS)
Protective effect of pulmonary surfactant on elastase-induced emphysema in mice
Authors: Otto-Verberne CJ , Ten Have-Opbroek AA , Franken C , Hermans J , Dijkman JH
Published: November 2022

The aim of this study was to obtain some evidence of a protective role for pulmonary surfactant in the pathogenesis of emphysema. Firstly, we developed a quick and easy method to treat mice with a series of intratracheal instillations. Subsequently, three groups of mice were treated as follows: two groups received intratracheal instillations with pancreatic elastase (1.8 mg.kg-1 BW) followed after 3, 48 and 96 h in one group (El/Surf group) by intratracheal administration of surfactant (100 mg phospholipid.kg-1 BW), and in the other group by instillations with saline (El/s group). The third group of control mice was treated with saline followed by three doses of surfactant (s/Surf group). After eight weeks, the mice were killed and emphysema was measured by calculating the mean linear intercepts (Lm) of airspaces. The Lm values in the different groups were statistically tested for differences by the Mann-Whitney test. Instillation of pancreatic elastase (El/s group) resulted in an evenly distributed increase in Lm compared with the control group. Administration of surfactant in elastase-treated mice (El/Surf group) resulted in a statistically significant inhibition of airspace enlargement. Although the Lm in the El/Surf group was still higher than in the control group, analysis of histograms of Lm values per field of examination revealed that the Lm distribution in the former group was similar to that of the s/Surf group. The El/s group, on the contrary, showed the presence of many fields with enlarged air spaces. Repeated instillations with saline and/or surfactant had no effect on the Lm.(ABSTRACT TRUNCATED AT 250 WORDS)
Tumour-like presentation of pulmonary sarcoidosis
Authors: Abramowicz MJ , Ninane V , Depierreux M , de Francquen P , Yernault JC
Published: November 2022

We report a case of pulmonary sarcoidosis, which initially presented as a left apical infiltrate. The later course mimicked a pulmonary neoplasm, with left upper lobe atelectasis secondary to bronchial stenosis, resulting from both endobronchial sarcoidosis and extrinsic compression by enlarged lymph nodes. Extrinsic pressure from sarcoid nodes on the left main pulmonary artery and recurrent laryngeal nerve, also caused a reduction in pulmonary parenchymal perfusion and left vocal cord paresis.