bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron content in human alveolar macrophages
Authors: Corhay JL , Weber G , Bury T , Mariz S , Roelandts I , Radermecker MF
Published: November 2022

Intracellular iron can be estimated semi-quantitatively by histochemical determination using the ferrocyanide reagent's score. Particle-induced X-ray emission (PIXE) allows accurate determination of various elements including iron in cells and biological fluids. Both techniques have been used to measure iron in alveolar macrophages gathered by bronchoalveolar lavage. The purpose of this study was to investigate the clinical usefulness of the PIXE technique in occupational respiratory medicine and in various pulmonary diseases. Using the PIXE method, we measured the iron content of alveolar macrophages in healthy subjects, with and without occupational exposure to iron dust, and in patients with pulmonary diseases (chronic obstructive pulmonary disease (COPD), lung cancer, Goodpasture's syndrome). Our results were then compared with those obtained with the ferrocyanide reagent. Intramacrophagic iron was 0.33 +/- 0.21 micrograms.10(-6) (mean +/- SD) cells in healthy non-smoking subjects without occupational exposure. Intramacrophagic iron was increased in smokers, iron-steelworkers, and in patients with COPD or lung cancer even in the absence of pulmonary haemorrhage. The two patients with Goodpasture's syndrome had high intramacrophagic iron content. About 80% of the whole bronchoalveolar lavage fluid iron content was in the cells. Mean iron content of blood monocytes, lymphocytes and neutrophils of eight healthy subjects was significantly lower than that of alveolar macrophages. A significant correlation was found between iron determination by the PIXE method and the ferrocyanide reagent's score (r = 0.89). We conclude that intramacrophagic iron may be increased in steelworkers and subjects with pulmonary haemorrhage, but also in asymptomatic smokers, in COPD and lung cancer patients without occupational exposure to iron dust.
Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects
Authors: Montefort S , Roche WR , Howarth PH , Djukanovic R , Gratziou C , Carroll M , Smith L , Britten KM , Haskard D , Lee TH , et al.
Published: November 2022

Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T-lymphocytes in allergic inflammation in asthma. There is evidence suggesting that the expression of adhesion molecules on endothelial cells and of their receptors on leucocytes is involved in this process. To investigate these mechanisms we have obtained bronchial mucosal biopsies from 10 normal subjects and from 10 symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6 weeks of inhaled beclomethasone dipropionate (BDP) during which time their clinical response was monitored. Frozen sections were stained by the immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium and ELAM-1 in endothelium, with no significant differences being apparent between the asthmatic and normal subjects. Topical BDP markedly reduced the mucosal eosinophilia without affecting the expression of either adhesion molecule. Using this method, we conclude that there is basal expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not significantly different from that in asthmatics, and that it is insensitive to suppression with corticosteroids at an inhaled dose that causes clinical improvement.
Bronchial responsiveness and work-related asthma in aluminium potroom workers: effect of removal from exposure
Authors: Soyseth V , Kongerud J , Boe J , Fonneland T
Published: November 2022

Twelve subjects relocated from aluminium potrooms due to work-related asthma were followed up for 2-27 months (median 23 months). Repeated post-relocation examinations (numbering 3-7, median 6) of methacholine challenge, forced expiratory volume in one second (FEV1), eosinophil cell count and respiratory symptoms were carried out at regular intervals. At the time of relocation, bronchial hyperresponsiveness (provoking concentration producing a 20% fall in FEV1 (PC20) less than or equal to 8.0 mg.ml-1) was found in eight of the subjects. During the follow-up period a twofold increase in PC20 was found in 7 of the 8 subjects who had PC20 less than 8.0 mg.ml-1 at the time of relocation. There was an improvement of symptoms but no improvement in FEV1 or decrease of eosinophils during the follow-up examinations.
Diurnal variation in FEV1 after heart-lung transplantation
Authors: Morrison JF , Higenbottam TW , Hathaway TJ , Clelland C , Scott JP , Wallwork J
Published: November 2022

We have examined the diurnal variation in forced expiratory volume in one second (FEV1) in 25 heart-lung transplantation patients over a four week period in order to study the pathophysiological mechanisms underlying the increased mortality and morbidity which occurs at night in asthma. These patients do not have pulmonary autonomic nervous reflexes, but often have muscarinic receptor hypersensitivity. They also develop mixed cell infiltration of the lung tissue in the course of infection or rejection. Thus, they show many features in common with asthma. Seventeen patients (68%) showed a significant diurnal variation in airway calibre (mean amplitude of FEV1 was 4.6% (SD 3.7%)), which is similar to that reported in normal adults. One patient had a diurnal variation of 34.5% during an episode of rejection. This variation fell to 6.9% after steroid therapy, a change often seen in asthma. There was a correlation between increased amplitude of the variation and the presence in transbronchial biopsies of airway submucosal eosinophils and lymphocytes, associated with a histological diagnosis of acute rejection and with epithelial damage. No association was seen with muscarinic receptor sensitivity. The variation in FEV1 showed no alteration from the normal day/night synchronization, and the peak values were around 1300 h. We conclude that the diurnal variation in FEV1 after heart-lung transplantation is not dependent on autonomic nerve reflexes or muscarinic receptor sensitivity, but is related to the consequences of inflammation described above.
Changes in heart rate during obstructive sleep apnoea
Authors: Andreas S , Hajak G , von Breska B , Ruther E , Kreuzer H
Published: November 2022

The mechanisms behind the decrease in heart rate during apnoeas in patients with obstructive sleep apnoea (OSA) are little known. Recent findings in animal experiments indicate that stimulation of the upper airway activates postinspiratory and cardiac vagal neurones in the medullary respiratory centre, causing alterations in heart rate and respiratory rhythm. Since OSA leads to a collapse of the airway and consequent stimulation of upper airway receptors, we studied the interrelations between heart rate and respiratory rhythm during apnoea and during negative intrathoracic pressure generated by the Mueller manoeuvre (MM). Fifteen patients with OSA (apnoea hypopnoea index (AHI) 45 +/- 28.h-1) were studied by polysomnography, during a MM and a Valsalva manoeuvre, each of 15 s duration. The heart rate decrease (delta HRA) and the increase in total respiratory cycle duration (TOT) were evaluated during apnoea in non-rapid eye movement (REM) sleep. Patients with OSA demonstrated a decrease in heart rate during apnoea (-14.4 +/- 9.0 beats.min-1), and during MM (-11.5 +/- 13.5 in OSA vs 3.1 +/- 7.8 beats.min-1 in a control group). TOT increased during apnoea (4.6 +/- 3.1 s). There was a significant correlation between delta HRA and AHI (r = -0.64) as well as between delta HRA and increase in TOT (r = 0.62). These findings indicate that upper airway obstruction may cause an activation of receptors at the site of airway collapse or distortion leading to changes in heart rate and respiratory rhythm.
Haemodynamic effects of short-term nasal continuous positive airway pressure therapy in sleep apnoea syndrome: monitoring by a finger arterial pressure device
Authors: Sforza E , Capecchi V , Lugaresi E
Published: November 2022

We have evaluated the effects of short-term nasal continuous positive airway pressure (nCPAP) therapy on systemic blood pressure and heart rate in patients with obstructive sleep apnoea syndrome. Twenty five consecutive patients were examined during baseline conditions (No-CPAP) and during one night of nCPAP treatment (CPAP). The mean value and the variation coefficient of cardiovascular variables, examined by a finger arterial pressure device (Finapres), were determined in wakefulness and sleep. Without nCPAP an increase in blood pressure from wakefulness to sleep was observed in all patients from 138 +/- 3 mmHg to 146 +/- 3 and 155 +/- 4 mmHg, and from 80 +/- 1 mmHg to 82 +/- 2 and 84 +/- 2 mmHg, respectively, for systolic and diastolic values in non rapid eye movement (NREM) and rapid eye movement (REM) sleep. Conversely, heart rate decreased from 75 +/- 2 beats.min-1 to 70 +/- 2 and 69 +/- 2 beats.min-1. In addition, variability of heart rate and blood pressure was greatly increased compared with the awake state. Short-term nCPAP therapy significantly reduced systolic pressure from 144 +/- 3 mmHg to 137 +/- 3 and 143 +/- 4 mmHg during NREM and REM sleep, respectively, associated with a decrease in heart rate (from 69 +/- 2 to 65 +/- 2 beat.min-1). In total sleep and in all sleep stages a significantly reduced variability (p less than 0.001) was found. No changes were observed for diastolic pressure during CPAP night compared with baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory function during wakefulness and sleep among survivors of respiratory and non-respiratory poliomyelitis
Authors: Dolmage TE , Avendano MA , Goldstein RS
Published: November 2022

The purpose of this study was to determine whether there is a difference in respiratory mechanics and gas exchange between polio survivors and healthy, age-matched controls during wakefulness and sleep. Polio survivors were divided into four groups. The first group included those who had evidence of respiratory muscle involvement originally (PRM) and the second group included those who had bulbar muscle involvement originally (PBM). The third and fourth groups had only limb involvement originally but were separated by absence (PSL) or presence of a scoliosis (PSS) at the time of their evaluation. Each subject completed baseline and one year follow-up measurements of lung volumes, diffusion, flow rates, respiratory muscle strength, central and peripheral chemoreflexes and arterial blood gases. Sleep measurements included a full respiratory polysomnographic study. Fifty polio survivors and 13 controls completed the study. The PRM and PSS groups had an elevated arterial carbon dioxide tension (PaCO2) (mean +/- SE 6.0 +/- 0.4 and 6.0 +/- 0.3 kPa, respectively), reduced vital capacity (2.8 +/- 0.3 and 2.9 +/- 0.3 l, respectively), reduced maximal inspiratory pressure (-5.9 +/- 0.7 and -5.4 +/- 0.8 kPa, respectively) and reduced maximal expiratory pressure (9.8 +/- 1.1 and 9.1 +/- 1.2 kPa, respectively), when compared with non-polio controls. During sleep PRM and PSS groups experienced a higher PaCO2 (6.5 +/- 0.5 and 6.7 +/- 0.4 kPa, respectively) and a lower arterial oxygen saturation (SaO2) (89 +/- 4 and 86 +/- 3%, respectively). There were no differences among groups for diffusion, flow rates and chemoreflexes. All other polio survivors showed essentially normal respiratory function.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung volumes measured by the forced rebreathing technique in children with airways obstruction
Authors: Merkus PJ , Verver S , van Essen-Zandvliet EE , Duiverman EJ , Kerrebijn KF , Quanjer PH
Published: November 2022

Forced rebreathings may recruit trapped gas into the mixing process. Therefore, we assessed the validity and reproducibility of measurements of residual volume (RVN2) by forced rebreathing in a closed circuit using N2 as indicator gas (N2FR) in children with airways obstruction. Validity was studied from measurements of RV obtained by N2FR, by helium dilution during resting ventilation, and by body plethysmograph at low panting frequency in young patients (8-18 yrs, 13 with asthma, forced expiratory volume in one second (FEV1) 93.0 +/- 22.8% pred; 12 with cystic fibrosis (CF), FEV1 80.4 +/- 16.4% pred). Reproducibility of RVN2 was assessed from duplicate measurements in 73 patients with asthma before and after bronchodilation (FEV1 81.4 +/- 13.7 and 99.6 +/- 11.5% pred, respectively), and in nine patients with CF; the total lung capacity (TLC) was unaffected by bronchodilation; 3,797 +/- 830 ml and 3,807 +/- 843 ml, respectively. Gas dilution methods gave comparable results in all subjects but gave lower values than plethysmography in patients with cystic fibrosis. Reproducibility was satisfactory, median differences between duplicate measurements of RVN2 and TLCN2 varying between 13 and 46 ml, respectively. We conclude that N2FR is quickly performed and well-tolerated. Lung volumes are highly reproducible and agree well with those obtained with the helium dilution method. Deep inspirations do not seem to overcome gas trapping in patients with CF.
Intraventricular rifampicin in severe tuberculous meningo-encephalitis
Authors: Vincken W , Meysman M , Verbeelen D , Lauwers S , D'Haens J
Published: November 2022

We present a patient acutely ill from severe tuberculous meningo-encephalitis, in whom acute hepatic and renal failure, due to intercurrent septic shock, precluded the administration of full systemic dosage of antituberculous drugs. Daily direct intraventricular administration of 5 mg rifampicin, via a subcutaneous Ommaya reservoir connected to a catheter placed in the right lateral cerebral ventricle, resulted in rapid improvement without neurological sequelae. Intraventricular rifampicin administration for 50 consecutive days was well-tolerated without local or systemic side-effects. In well-selected patients with severe tuberculous meningo-encephalitis, intraventricular rifampicin may safely and highly effectively be added to systemic antituberculous therapy.
Inhaled steroids modify bronchial responses to hyperosmolar saline
Authors: Rodwell LT , Anderson SD , Seale JP
Published: November 2022

We investigated the effects of inhaled beclomethasone dipropionate (BDP) on airway sensitivity (provocative dose producing a 20% fall in forced expiratory volume in one second (FEV1) from baseline (PD20)) and reactivity (slope of the dose-response curve) to inhaled aerosols of hyperosmolar (4.5%) saline, and histamine or methacholine. This was an open study on 13 patients referred to the laboratory by their respiratory physician for investigation of their asthma. These challenges were performed on separate days before (initial visit) and 8.8 +/- 0.8 (SD) weeks (range 5.6-12.4 weeks) after (visit 1) a treatment period with BDP (dose range 600-1,500 micrograms.day-1). At visit 1 there was a significant reduction in sensitivity to 4.5% NaCl and histamine/methacholine and in reactivity. The PD20 increased 5.6 fold for 4.5% NaCl and 4.1 fold for histamine/methacholine. All patients remained responsive to histamine/methacholine and a fall in FEV1 > 20% to 4.5% saline was documented in 10 of the 13 patients. We conclude that treatment with BDP reduces sensitivity and reactivity to both osmotic and pharmacological challenge.
Lipopolysaccharide (LPS) inhalation in healthy subjects increases neutrophils, lymphocytes and fibronectin levels in bronchoalveolar lavage fluid
Authors: Sandstrom T , Bjermer L , Rylander R
Published: November 2022

Bacterial endotoxin has been suggested as responsible for the development of subjective symptoms and transient or chronic lung function impairment seen after exposure to organic dusts in cotton mills, poultry houses, swine confinement buildings and saw mills. Animal experiments have demonstrated bronchoalveolar neutrophilia being the most prominent cell response in animals following bacterial lipopolysaccharide (LPS) inhalation. The present study was conducted to obtain information on some aspects of the early inflammatory response to inhaled LPS in man. Eight healthy nonsmoking subjects, 23-27 yrs old, underwent bronchoalveolar lavage (BAL), 3 h after a provocation test with 100 micrograms LPS from E. coli dissolved in 2 ml isotonic NaCl. The solution was aerosolized with a jet nebulizer and inhaled. The calculated dose delivered to the lung was approximately 25 micrograms, which equals exposure in some occupational settings. The BAL data for each individual subject were compared with data from a control BAL performed at least 6 weeks prior to the LPS challenge. The major cellular response to LPS, reflected in BAL fluid, was an approximately hundredfold increase in neutrophils. The total number of lymphocytes was on average tripled. The alveolar macrophage phagocytosis of opsonized yeast particles in vitro was significantly reduced. A further indicator of an ongoing inflammation was an increase in fibronectin. No changes were seen in the levels of BAL albumin, indicating that the elevated level of fibronectin could not be explained by an increased permeability, but rather by a local production. The results correspond with data from animal studies and further supports the hypothesis that bacterial LPS is important in the pulmonary reaction induced by organic dusts.
Comparison of nebulized and intravenous terbutaline during exacerbations of pulmonary infection in patients with cystic fibrosis
Authors: Finnegan MJ , Hughes DV , Hodson ME
Published: November 2022

Twenty three patients completed a double-blind study, comparing intravenous and nebulized terbutaline, during the first four days of a pulmonary exacerbation of cystic fibrosis (CF), with follow-up to day 10. Routine treatment with chest physiotherapy and appropriate intravenous antibiotics was given to all patients. The best peak flow rate (PF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), in the past year and at entry to the study, revealed no significant difference between the groups. However, on day 10, PF, FEV1 and FVC, of the nebulizer group remained significantly reduced compared to best values in the previous year, whereas the PF and FEV1 in the intravenous group were not significantly reduced compared to the best values in the previous year. Comparison of regression lines showing the overall rate of improvement of PF, FEV1 and FVC between the two groups showed that the rate of improvement of each parameter was more rapid in the group receiving intravenous terbutaline. This was statistically significant for PF. It is possible that during acute exacerbations of infection, sputum retention makes it more difficult for the inhaled bronchodilators to reach the airways and intravenous therapy is, therefore, more beneficial.
Comparison of nebulized and sprayed topical anaesthesia for fibreoptic bronchoscopy
Authors: Keane D , McNicholas WT
Published: November 2022

We compared the efficacy of nebulized (N) and sprayed (S) topical anaesthesia prior to fibreoptic bronchoscopy in a blinded study involving 54 patients aged 57 +/- 26 yrs (mean +/- SD). Cough frequency, recorded on cassette tape, was the index of efficacy. All patients received 100 mg lignocaine sprayed into the pharynx, or nebulized in random order prior to bronchoscopy, and all received intravenous diazepam sedation. Each patient received a further 100 mg of lignocaine solution through the bronchoscope onto the vocal cords and major airways during the procedure. No significant difference was found in overall cough frequency between N and S groups (8.7 +/- 6.9 coughs.min-1 N vs 10.5 +/- 6.0 S), and cough frequency was also similar between N and S during the periods above and below the vocal cords. Furthermore, no differences were found in cough frequency between N and S among smokers, patients with asthma and COPD, and patients who had a biopsy procedure, although a trend was seen in all comparisons towards a lower cough frequency with the nebulized route. Most patients in the S group found the spray unpleasant, whereas only one in the N group complained. We conclude that nebulized and sprayed lignocaine have similar efficacy as topical anaesthetics in fibreoptic bronchoscopy, but patient preference favours the nebulized route.
Antihistamines in the treatment of asthma
Authors: Bousquet J , Godard P , Michel FB
Published: November 2022

Histamine is an important mediator of asthma. The new anti-histamines which block histamine at the H1-receptor level also possess some anti-allergic properties. At current dosages they appear to be safe. These drugs are effective in the treatment of rhinitis and conjunctivitis but their role in asthma is still under investigation. At a dose higher than usually recommended, they were shown to block exercise-induced asthma and, inconstantly, the early phase reaction after allergen challenge. Their effect on the late phase allergic reaction as well as their clinical efficacy during trials is, however, less consistent. The indication of H1-blockers in the treatment of asthma is therefore limited, especially since doses higher than recommended may lead to adverse reactions.
Modulation by theophylline and enprofylline of the excitatory non-cholinergic transmission in guinea-pig bronchi
Authors: Barlinski J , Lockhart A , Frossard N
Published: November 2022

The mechanism of action of xanthines in asthma remains controversial. Since sensory innervation may play a role in the pathogenesis of asthma, we investigated whether xanthines were capable of reducing the contractile response of the bronchi to nerve stimulation. In guinea-pig bronchi in vitro, electrical field stimulation (EFS: 40 V, 16 Hz, 0.2 ms during 10 s) induces a rapid cholinergic contraction followed by a long-lasting contraction due to a local release of neuropeptides from C-fibre endings. We measured isometric neuronally-mediated contractions of bronchial smooth muscle and studied the effects of increasing concentrations of two xanthine derivatives, theophylline, an antagonist of adenosine receptors, and enprofylline, which has no effect on adenosine receptors. Both enprofylline (1-50 microM) and theophylline (10-100 microM) inhibited, in a concentration-dependent manner, the peptidergic contraction, an effect which was more marked with enprofylline than theophylline (EC50 = 9.6 +/- 0.7 microM and 62.0 +/- 4.7 microM, respectively). Conversely, the cholinergic response was unaffected. Contractions induced by exogenous substance P (0.03-3 microM) were also unaffected by theophylline and enprofylline at the above mentioned EC50s. Our results suggest that concentrations of theophylline, similar to those used therapeutically, reduce the release of sensory neuropeptides from C-fibre endings. This effect is unrelated to adenosine receptor blockade, since enprofylline had a similar inhibitory effect.
Gas exchange during simulated airway secretion in the anaesthetized rabbit
Authors: Lagerstrand L , Dahlback M , Hedenstierna G
Published: November 2022

We wished to study the effect of airways secretion on gas exchange. Peripheral airway secretion was simulated in 9 rabbits by the continuous inhalation of nebulized isotonic saline, at a droplet size of about 3 microns. Intrapulmonary deposition of saline in the peripheral airways (83% in airways smaller than 0.5 mm) did not alter total inspiratory resistance (mean 5.4 kPa.l-1.s), but led to a decrease in compliance of the total respiratory system from 45.9 to 21.8 ml.kPa-1 after one hour of nebulization. Arterial oxygen tension decreased from 17.8 kPa to 12.1 and 6.9 kPa after 5 and 60 min of nebulization, respectively. PaCO2 was unaffected after 5 min (4.5 kPa) but increased to 7.0 kPa after 60 min of nebulization. Ventilation-perfusion relationships (VA/Q) showed a significant increase in perfusion of areas with low VA/Q ratios (from 0.7 to 6.3% of cardiac output) and in shunt (from 1.4 to 4.3%) after 5 min of nebulization. At the end of the experiment shunt was increased markedly to 29.7% of cardiac output whereas perfusion of low VA/Q regions remained at the same level (7.3%). The results from this animal model indicate that all gas exchange abnormalities known to occur in asthma can be reproduced without measurably increasing the resistance of the respiratory system.
Clara cell protein in serum and bronchoalveolar lavage
Authors: Bernard A , Marchandise FX , Depelchin S , Lauwerys R , Sibille Y
Published: November 2022

The 10 kDa Clara cell protein was measured in serum and bronchoalveolar lavage (BAL) from 39 healthy subjects (14 smokers, 25 nonsmokers) and from 41 patients with respiratory disease (chronic obstructive pulmonary disease (COPD), sarcoidosis, lung cancer). Clara cell protein appears as one of the most abundant respiratory tract derived proteins, with values averaging 7% of the total protein content of lung lavages from healthy nonsmokers. A significant reduction of Clara cell protein was found in BAL from smokers and patients with COPD or lung cancer. The same pattern of change was found in the concentrations of Clara cell protein in serum. Pulmonary sarcoidosis did not affect absolute values of Clara cell protein in lung lavages but was associated with elevated levels in serum. Changes in lung lavage Clara cell protein differed from that of albumin, beta 2-microglobulin or the secretory component, since the latter were unaffected by smoking or COPD but increased in sarcoidosis and lung cancer. These results indicate that Clara cell protein in BAL or serum might serve as a sensitive indicator of nonciliated bronchial cell dysfunction.
Nasal and paranasal disease in adult cystic fibrosis patients
Authors: Kerrebijn JD , Poublon RM , Overbeek SE
Published: November 2022

Children with cystic fibrosis frequently have nasal polyps and sinusitis. This study addresses (para-) nasal disease in 39 adult cystic fibrosis patients. Fifteen patients (39%) had recently had serious nasal symptoms and 26% sinusitis. Seventeen (44%) had nasal polyposis. Almost all sinus radiographs taken showed opacification, which was unrelated to symptoms. Polypectomies and antral irrigations were usually ineffective, whilst more extensive surgery generally gave better results. It is concluded that a substantial number of adult cystic fibrosis patients frequently have upper airway symptoms. Sinus radiographs have little or no diagnostic value. Treatment of (para-) nasal disease in cystic fibrosis patients can be difficult; a guideline for treatment is suggested, calling for simple interventions coupled with intranasal steroids and nasal irrigation in early disease and for endoscopic to radical sinus surgery in recurrent advanced disease.
Comparison of inspiratory effort in sniff-like aspiration reflex, gasping and normal breathing in cats
Authors: Tomori Z , Donic V , Kurpas M
Published: November 2022

The changes in airway occlusion pressure and airflow, occurring during two spasmodic breathing patterns, were studied and compared with normal breathing pattern in 12 anaesthetized cats. The inspiratory effort developed during the sniff-like aspiration reflex elicited by mechanical stimulation of the nasopharynx under control conditions proved to be very similar in character and intensity to the activity observed during gasping which occurred on resuscitation, of the same cats, from hypoxic apnoea. The starting (P50) and maximum (Pmax) airway occlusion pressure developed in these two spasmodic breathing patterns were very high. Extremely rapid rates of contraction and relaxation were detected by computer-assisted measurements of dynamic changes in both the pressure values and the slopes of pressure curves. The results suggest common effector mechanisms, reflecting similar forceful inspiratory drives, for the aspiration reflex and gasping. These two spasmodic processes differ substantially from normal breathing. Nevertheless, the aspiration reflex differs from gasping in that it can be elicited by activation of upper airway afferents during eupnea. Moreover, as yet, there is no definitive evidence that the brainstem mechanisms responsible for generating the aspiration reflex are the same as those of the gasp. The main benefits of this reflex are its rather easy elicitability under various conditions and its capability to induce important cardiorespiratory effects (e.g.) reversal of central apnoea) owing to its powerful activity.
Ferret tracheal mucus rheology, clearability and volume following administration of substance P or methacholine
Authors: De Sanctis GT , Rubin BK , Ramirez O , King M
Published: November 2022

We studied the effects of substances P administration on tracheal mucus viscoelasticity, water content, clearability and secretion rate. Six neutered adult male ferrets (weight 1.1-1.5 kg) were studied, on four occasions each. They were anaesthetized with ketamine and xylazine, and intubated shallowly. Control mucus (pre- and post-Ringer instillation) was compared with the mucus obtained following instillation of 200 microliters of 10(-6), 10(-5), and 10(-4) M substance P (SP), and 10(-4) M methacholine chloride as a reference. Tracheal mucus was collected by inserting a soft-bristled cytology brush to the level of the carina, and leaving it in contact with the mucosa for 30 min. After withdrawing the brush, the adherent mucus was quickly scraped off and layered with paraffin oil to prevent evaporation. The mucus was analysed for viscoelasticity by magnetic rheometry and solids content by evaporation to dryness. Mucus transportability was assessed by comparison with model gels, and also by means of the frog palate assay, which indicates how well mucus is cleared by normal ciliary action. There was a dose-related increase in mucus volume, and a dose-related decrease in mucus viscosity and elasticity, with substance P administration. Mucus transportability increased with both substance P and methacholine. The effects of 10(-4) SP and methacholine were comparable in terms of viscoelasticity and volume; with both methacholine and SP, there appeared to be an additive effect. The mucus solids content did not correlate with the viscoelastic changes for SP administration, whereas it did for methacholine. These observations suggest that the hypersecretion induced by these two agents might involve different pathways.
Increased lung to blood passage of polyethylene glycols after intratracheal instillation of ferritin and asbestos fibres in the rat
Authors: Folkesson HG , Leanderson P , Westrom BR , Tagesson C
Published: November 2022

Urinary recovery of intratracheally instilled polyethylene glycol polymers (PEG:s) in the molecular weight range 722-1294 Da (PEG 1000) was studied under normal conditions and during experimentally induced lung damage in rats. The urinary PEG recoveries were between 30-60% under normal conditions, with a selectivity for smaller PEG:s. No significant differences in the urinary PEG molecular weight profiles were found between 30 days old and adult rats; i.e. they had similar PEG 1162/810 (molecular weights) urinary recovery ratios (0.78 +/- 0.25 and 0.69 +/- 0.27, respectively, p > 0.05). In rats instilled with PEG 1000 and ferritin (5 mg.kg-1 body weight), the urinary recovery was increased for PEG:s with molecular weights greater than 1030 Da; i.e. a higher PEG 1162/810 recovery ratio (1.44 +/- 0.58, p < 0.01) was obtained. Rats instilled with PEG 1000 and crocidolite asbestos fibres (5 mg.kg-1 body weight) showed higher urinary recoveries for PEG:s greater than 854 Da, resulting in a higher PEG 1162/810 ratio (1.47 +/- 0.59, p < 0.01). By adding the iron-chelator, desferrioxamine, to the crocidolite-instillate, the urinary recoveries and the PEG 1162/810 ratio (0.97 +/- 0.47) were reduced, indicating a restored molecular weight selectivity of the lung. Thus, in rats, PEG 1000 passes via the respiratory tract in large amounts which is dependent on the molecular weight. This passage was increased after ferritin- or crocidolite instillation, indicating that the barrier function of the respiratory tract was impaired due to local tissue damage, and that iron may play an important role in this.
Changes in epithelial lining fluid albumin associated with smoking and interstitial lung disease
Authors: Roberts CM , Cairns D , Bryant DH , Burke WM , Yeates M , Blake H , Penny R , Shelley L , Zaunders JJ , Breit SN
Published: November 2022

Albumin is an important plasma protein which is useful in the assessment of in vivo membrane permeability in the lung. In subjects with interstitial lung disease (ILD) the relationship between albumin recovered from bronchoalveolar lavage (BAL) and other markers of inflammatory activity may provide useful information of the pathogenesis of the disease process. Unfortunately, its measurement is hampered by the variable dilution in BAL fluid. In this study, urea was used as a marker of epithelial lining fluid (ELF) dilution allowing the calculation of an apparent epithelial lining fluid volume and adjusted albumin content. We examined the relationship between ELF albumin content and BAL cell counts, immunoglobulin content, respiratory function tests and gallium lung scans in both smokers and nonsmokers with and without interstitial lung disease. Forty seven subjects with connective tissue disease and interstitial lung disease and 51 subjects with either connective tissue disease but no pulmonary involvement or non pulmonary malignancy (18 current smokers) underwent BAL, gallium lung scans and respiratory function tests. The subjects with ILD were further subdivided into those with active ILD or bronchiolitis using cluster analysis. In smokers without ILD an increased ELF volume and a decrease in ELF albumin were found. Increased ELF albumin was related to increased age. In subjects with ILD, increased albumin was strongly correlated with increased BAL lymphocyte absolute and differential counts, which overwhelmed any age or smoking effect. These findings suggest a possible causal relationship between lung vascular permeability and lymphocyte numbers in subjects with interstitial lung disease and reinforce the need to consider smoking and age as confounding factors in BAL analysis.
Inhalation of nitric oxide modulates methacholine-induced bronchoconstriction in the rabbit
Authors: Hogman M , Frostell C , Arnberg H , Hedenstierna G
Published: November 2022

Nitric oxide (NO) accounts for the major effects of endothelium-derived relaxing factor. We investigated whether NO, added to the inspired gas, could exert a bronchodilatory action similar to the pulmonary vasodilation described when administering NO during lung vascular constriction. New Zealand White rabbits were intubated and mechanically-ventilated with 30% oxygen during neuroleptanaesthesia. Methacholine (MCh) was nebulized at increasing concentrations from 0.5 to 4.0 mg.ml-1, with or without inhalation of 80 parts per million (ppm) NO. The technique of rapid airway occlusion during constant-flow inflation was used for measuring respiratory mechanics, i.e. resistance and compliance of the respiratory system. Methacholine nebulization without NO inhalation raised the resistance from 51 +/- 6 (mean +/- 95% confidence interval) to 107 +/- 52 cmH2O.l-1.s at Mch 4 mg.ml-1. During NO inhalation, nebulization of MCh showed no significant increase in resistance. Arterial oxygen tension (PaO2) and compliance fell to the same extent during methacholine challenge, whether NO was inhaled or not. Closure of small airways may be a mechanism that causes the decrease in PaO2 and compliance observed. This suggests that 80 ppm NO added to the inspired gas modulates the response in central airway tone to nebulized MCh in this rabbit model. However, it appears to have less effect on peripheral airways.
Is lung retransplantation indicated? Report on four patients
Authors: Shennib H , Novick R , Mulder D , Menkis A , Morin JF , McKenzie N , Kaye M , Noirclerc M
Published: November 2022

As more lung transplantations are performed, many patients will suffer graft failure and will be considered for retransplantation. This article reviews the case management reports of four patients who received lung or heart/lung retransplantation, with overall disappointing results. The pros and cons of lung retransplantation are discussed.
Effects of intrinsic PEEP on pulmonary gas exchange in mechanically-ventilated patients
Authors: Brandolese R , Broseghini C , Polese G , Bernasconi M , Brandi G , Milic-Emili J , Rossi A
Published: November 2022

The aim of the study was to assess the impact of the intrinsic positive end-expiratory pressure (PEEPi) on pulmonary gas exchange in mechanically-ventilated patients, by comparing the effects of similar levels (0.8-0.9 kPa) of positive end-expiratory pressure (PEEP) and PEEPi. Ten patients with acute respiratory failure, without chronic airway disease, were studied with three ventilatory modes: 1) intermittent positive pressure ventilation with zero end-expiratory pressure (ZEEP mode); 2) continuous positive pressure ventilation with PEEP set by the ventilator (PEEP mode); and 3) intrinsic PEEP elicited by adequate shortening of the expiratory time (PEEPi mode). Cardiorespiratory variables (e.g. respiratory compliance and resistance, arterial and mixed venous blood gases, cardiac output, pulmonary capillary pressure, oxygen delivery) were measured during each ventilatory mode. Compared to ZEEP, both PEEP and PEEPi decreased cardiac output while increasing arterial oxygen tension (PaO2). However, the improvement of PaO2 was more consistent (8 out of 10 patients), and larger (+2.1 kPa, on average, p < 0.05) with PEEP than with PEEPi (5 out of 10 patients, and +1.4 kPa, on average, NS). Since the effects of PEEP and PEEPi on ventilation, lung volume, compliance, cardiac output (QT), mixed venous oxygen tension (PvO2) and oxygen consumption (VO2) were similar, we attributed the less favourable impact of PEEPi on PaO2 to a less homogeneous distribution of PEEPi between lung units with different time constant, and hence to a more uneven distribution of the inspired gas.
Comparison of nasal pressure support ventilation with nasal intermittent positive pressure ventilation in patients with nocturnal hypoventilation
Authors: Restrick LJ , Fox NC , Braid G , Ward EM , Paul EA , Wedzicha JA
Published: November 2022

Nasal intermittent positive pressure ventilation (NIPPV) provides effective ventilatory support in patients with nocturnal hypoventilation. Nasal pressure support ventilation (NPSV), which only provides ventilation in response to patient triggering, may also be effective, simpler, and cheaper, but has not been evaluated. NIPPV and NPSV were compared in 12 patients with nocturnal hypoventilation, requiring domiciliary ventilatory support. The patients were studied on three consecutive nights, in random order: a control night without ventilation and a night on each mode of ventilatory support using the bilevel positive airway pressure (BiPAP) ventilator. Both NIPPV and NPSV significantly increased mean arterial oxygen saturation (SaO2) compared to the control night (NIPPV mean increase 4.1%; 95% confidence interval (CI) 2.2 to 6.1, NPSV 4.4%; CI 2.1 to 6.6) with no significant difference between the two modes. The percentage of the study night spent below 90% SaO2 was significantly reduced by both ventilator modes compared to the control night (median reduction on NIPPV 37%; CI -54 to -10, reduction on NPSV 31%; CI -53 to -9, with no significant difference between NPSV and NIPPV. NPSV was as effective as NIPPV in patients with nocturnal hypoventilation, which suggests that these patients are able to trigger the ventilator adequately. The lower cost of NPSV will make it accessible to more patients with chronic lung disease.
Bronchodilator effect of nebulized sodium cromoglycate in children born prematurely
Authors: Yuksel B , Greenough A
Published: November 2022

We wished to determine whether nebulized sodium cromoglycate (SCG) has bronchodilator effects in very young children. In 18 children born prematurely and studied at a median of 15 months of age, thoracic gas volume (TGV) and airways resistance (Raw), were measured and hence specific airways conductance (sGaw) was calculated before (baseline) and after nebulized saline, and then after sodium cromoglycate. sGaw improved significantly in 10 infants after SCG, compared to only in two following saline. These preliminary results suggest that nebulized SCG may have an acute bronchodilator effect in some children born prematurely.
Cysteinyl leukotrienes overproduction and mast cell activation in aspirin-provoked bronchospasm in asthma
Authors: Sladek K , Szczeklik A
Published: November 2022

In order to examine the hypothesis that in aspirin-induced asthma (AIA) cyclooxygenase inhibition is associated with enhanced release of leukotrienes (LTs), we measured urinary leukotriene E4 (LTE4) and 11-dehydro-thromboxane B2 (TXB2) (as a measure of cyclooxygenase production) following challenge with oral aspirin or inhaled methacholine, in 10 AIA patients. We also determined serum tryptase and eosinophilic catonic protein (ECP) levels, in order to evaluate mast cell and eosinophil activation. Urinary LTE4 excretion was increased sevenfold 4-6 h after aspirin challenge, while 11-dehydro-TXB2 decreased gradually reaching 50% baseline levels 24 h after challenge (p < 0.05). This was accompanied by a significant fall in blood eosinophil count at 6 h, and a tendency to a rise in ECP. The intensity of both LTE4 and 11-dehydro-TXB2 responses depended on the dose of aspirin used (p < 0.001, analysis of variance (ANOVA)). The accompanying maximum fall in forced expiratory volume in one second (FEV1) was not correlated with peak LTE4 levels. In contrast to aspirin, methacholine challenge producing comparable bronchial obstruction, did not alter eicosanoid excretion or serum tryptase or ECP levels. In a separate study, lysine-aspirin inhalation challenge was performed in seven AIA patients, four of whom had responded with a rise in serum tryptase to oral aspirin challenge. Challenge with inhaled aspirin led to similar bronchoconstriction as with oral challenge, but non-respiratory symptoms such as scarlet flush or rhinorrhea were absent, and serum tryptase levels remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of serous-like cells in the surface epithelium of human bronchioles
Authors: Rogers AV , Dewar A , Corrin B , Jeffery PK
Published: November 2022

The conductive airways of the mammalian lung are lined by several morphologically distinct cell types, both ciliated and non-ciliated. Of the non-ciliated secretory cells, mucous (goblet), Clara and neuroendocrine cells have been identified in adult human bronchiolar epithelium but, thus far, the serous cell has not. We have examined human membranous and respiratory bronchioles from macroscopically normal peripheral lung (n = 5 cases). For ultrastructural studies, a minimum of five nucleated, non-ciliated cell profiles, containing electron-dense secretory granules, were selected at random from both bronchiolar levels in each case, such that a total of 60 cells was examined. Data from the computer-aided image analysis of the cells indicated that two populations existed, differing in both granule area and granule number per cell p < 0.0005 by discriminant analysis. By visual inspection, the cells fell neatly into two groups: those which, were predominantly serous-like in type, and those which were "Clara". In the membranous bronchioles, serous-like cells had a mean(SEM) granule area per cell of 3.67(0.62) microns 2 and Clara cells 0.47(0.07) microns 2 (p < 0.001). Also, in the membranous bronchiole, the mean(SEM) number of granules in serous-like cells was 40(4.7) and in Clara cells 10(1.1) (p < 0.001). At the respiratory bronchiolar level, the corresponding means were similar to those of the membranous bronchioles and, likewise, serous and Clara cells were significantly different. Thus, our data, indicate that serous cells are present in the adult human bronchiole.
Effects of acetazolamide on overnight oxygenation and acute mountain sickness in patients with asthma
Authors: Mirrakhlmov M , Brimkulov N , Cieslicki J , Tobiasz M , Kudaiberdiev Z , Moldotashev I , Shmidt G , Zielinski J
Published: November 2022

The aim of the study was to assess effects of acetazolamide in prevention of acute mountain sickness (AMS) and on overnight oxygenation, in patients with asthma treated at the altitude of 3,200 m. Sixteen patients with asthma, 6 males and 10 females, mean age 32 yrs, were first investigated at low altitude (760 m). They presented with mild airways obstruction, normal arterial blood gases, and normal oxygenation at night studied by pulse oximetry. After initial investigations, patients were divided by random number into the treated (T) and control (C) groups of eight patients each. T group patients received acetazolamide, 750 mg daily for 2 days, before the ascent and on the first day at altitude (3,200 m). Symptoms of AMS developed in seven patients from group C and in three from group T. The overnight pulse oximetry, performed on the first night at altitude, revealed that group T patients had statistically higher (p < 0.05) initial, 91 vs 87%, mean, 90 vs 86%, and minimum, 84 vs 75%, arterial oxygen saturation than group C patients. Overnight pulse oximetry was repeated on the 5th, 10th and 17th day at altitude, and showed that in group C patients, from the 5th day onwards, oxygenation improved to the level observed in group T patients on the first night. We conclude that pretreatment with acetazolamide before the ascent prevented patients with asthma from developing symptoms of AMS, and alleviated acute changes in arterial oxygen saturation brought about by the high altitude hypoxia.
Assessment of the respiratory compliance in awake subjects using pressure support
Authors: Azarian R , Lofaso F , Zerah F , Lorino H , Atlan G , Isabey D , Harf A
Published: November 2022

Pressure support (PS), a new mode of ventilatory assistance, is known to induce respiratory muscle relaxation. It was used to obtain reliable measurements of the compliance of the respiratory system (Crs) in awake subjects. PS was applied, through a mouthpiece, at four successive levels (0, 0.75, 1 and 1.25 kPa) to 30 healthy subjects. At the highest PS level, the subject's relaxation was obtained as assessed by a decrease in the occlusion pressure from 0.10 +/- 0.06 to 0.05 +/- 0.04 kPa, whereas the minute ventilation increased (from 7.5 +/- 1.5 to 13.8 +/- 3.3 l.min-1), and the end-tidal carbon dioxide tension (PCO2) decreased (from 5.0 +/- 0.4 to 3.2 +/- 0.5 kPa) below its apnoea threshold. In three subjects, respiratory muscle relaxation was confirmed by a fall in diaphragmatic electromyographic activity. Crs was calculated as the ratio of the tidal volume to the corresponding end-inspiratory airway pressure (i.e. PS level) since, at end inspiration, a zero-flow period was obtained. Crs was highly correlated (r = 0.77) to the height (Ht) of the subjects: Crs (l.kPa-1) = 3.56 x Ht (m) -4.86 (+/- 0.23), allowing normal values to be determined. In order to evaluate the applicability of the method to patients, Crs was measured in four patients with scoliosis, and was found to range from 45-82% of the predicted values. It is suggested that this simple method of Crs determination may be used to characterize various chest wall or pulmonary diseases.