bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled expiration in mechanically-ventilated patients with chronic obstructive pulmonary disease (COPD)
Authors: Aerts JG , van den Berg B , Bogaard JM
Published: November 2022

In patients with severe chronic obstructive pulmonary disease (COPD), lung emptying may be affected by flow limitation. We tested the hypothesis that the airway compression leading to flow limitation can be counteracted by controlling the expiratory flow. The effects of an external resistor on lung emptying were studied in six patients with COPD, who were mechanically ventilated whilst sedated and paralysed. Respiratory mechanics were obtained during ventilatory support with and without the resistor. Airway compression was assessed using the interruptor method. For the study, a turbulent resistor was applied with the highest resistance level that did not increase the end-expiratory lung volume. At this resistance level, external positive end-expiratory pressure (PEEP) was generated in all patients. As total PEEP levels remained unchanged at both settings during the controlled expiration, the levels of intrinsic PEEP were significantly decreased from 0.96+/-0.30 to 0.53+/-0.19 kPa (mean+/-SD). Comparison of the expiratory flow-volume curves at both settings revealed that, during the controlled expiration, the flows were significantly decreased during the first 40% of the expired volume and significantly increased during the last 60%. As the end-expiratory lung volumes remained unchanged during both settings, these increments in flow indicated a decrease in effective resistance. Airway compression was observed during unimpeded expirations in all patients using the interruptor method. During the application of the resistor, airway compression was no longer detectable. In patients with chronic obstructive pulmonary disease receiving ventilatory support, the application of an external resistor could decrease effective expiratory resistance by counteracting airway compression, without increments in end-expiratory lung volume.
Damage to the nasopharyngeal mucosa induced by current levels of urban air pollution: a field study in lambs
Authors: Gulisano M , Marceddu S , Barbaro A , Pacini A , Buiatti E , Martini A , Pacini P
Published: November 2022

This study concerns the effects of urban air pollution on the nasopharyngeal epithelium, with the aim of evaluating the possible harmful activity of levels of atmospheric pollution which are not currently considered to be dangerous. Over a 3 month period, 10 lambs kept in a zone characterized by numerous vehicles were sacrificed at regular intervals, and their nasopharyngeal mucosa was examined by scanning electron microscopy and image analysis. Two lambs kept in a rural area were used as controls. The local levels of some airborne contaminants (NO(x), NO2, NO, SO2, CO and particulate matter with aerodynamic diameter < or =10 microm (PM10)) were monitored throughout the experiment. The urban air had an irritating effect, inducing hypersecretion of mucus and morphological damage to the ciliated epithelium. These alterations increased with the duration of exposure to urban air and with increasing pollution levels, although the levels remained below current legal levels. We conclude that the harmful effects of airborne contaminants are probably underestimated. Moreover, physicochemical evaluation of pollution parameters should be complemented by morphological study of upper respiratory epithelium in exposed animals, since this mucosa is a sensitive target for irritating agents.
Smoking cessation with a 16 h nicotine patch: results in a group of hospital workers
Authors: Jimenez Ruiz CA , Florez S , Ramos A , Ramos L , Solano S , Fornies E
Published: November 2022

As part of a programme for the implementation of a Smoking Control Policy in our hospital, an open study, without randomization, of 65 hospital workers, who wanted to give up smoking, was carried out. The characteristics of smoking in each subject were recorded. The Fagerstrom Questionnaire was used to measure the degree of dependence on nicotine. The treatment consisted of the daily use of 16 h nicotine patches for 12 weeks. During the first 4 weeks, the patches contained 15 mg of nicotine, for the second 4 weeks, 10 mg, and for the last 4 weeks 5 mg (per patch and day). Five visits were scheduled during the 26 week study period: at the start of the study and after 4, 8, 12 and 26 weeks. The abstinence was checked by measuring carbon monoxide in end-expiratory air. The success rate was 31% after 12 weeks, and decreased to 29% after 26 weeks. In conclusion, the nicotine patches appeared safe and effective in this study.
IL-5 production by bronchoalveolar lavage and peripheral blood mononuclear cells in asthma and atopy
Authors: Tang C , Rolland JM , Ward C , Quan B , Walters EH
Published: November 2022

There is increasing evidence to suggest a key role for interleukin-5 (IL-5) in the regulation of airway eosinophilia in asthma. We compared the capacity for IL-5 production in atopic asthmatic, nonatopic asthmatic, atopic nonasthmatic and normal subjects, and evaluated the usefulness of peripheral blood cells for reflecting airway cell reactivity. Bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) from 12 atopic and 10 nonatopic asthmatics (without inhaled steroid therapy), 9 atopic nonasthmatics, and 10 normal controls were cultured with or without house dust mite (HDM, 10 microg x mL-1) stimulation. CD4+ T-cell activation, IL-5 and interferon-gamma (IFN-gamma) production in the cultures were assessed. Both for BAL and PBMC samples, atopic and nonatopic asthmatic subjects showed comparable spontaneous production of IL-5, which was significantly higher than that either for atopic nonasthmatics or normal controls (p<0.05 or p<0.01). There was a significant correlation between the percentage of eosinophils in BAL and spontaneous production of IL-5 by BAL cells in both asthmatic groups (p<0.05 or p<0.01). Both these parameters were also associated with asthmatic airway narrowing as denoted by a negative relationship with baseline forced expiratory volume in one second (FEV1) as percentage predicted (p<0.05 and p<0.01, respectively). In contrast, IFN-gamma production by unstimulated BAL cells from normal controls was higher than that for BAL cell cultures of nonatopic asthmatic subjects (p<0.05). Following HDM stimulation, both atopic groups had comparable positive responses in terms of CD4+ T-cell activation, but there was relatively greater IL-5 production in asthmatic PBMC (p<0.05) and, in particular, BAL cell cultures (p<0.01). These findings suggest that elevated IL-5 production is a common feature of BAL cells and PBMC in atopic and nonatopic asthma. In addition, atopic asthmatics show greater IL-5 production in response to specific allergen compared with atopic nonasthmatics, an effect most marked in BAL cells compared to PBMC. Hence, peripheral blood mononuclear cells can reflect cytokine immunoreactivity of airway cells, but lack local cellular interactions, which limits their usage in asthma research.
Commercial plasma alpha1-antitrypsin (Prolastin) contains a conformationally inactive, latent component
Authors: Lomas DA , Elliott PR , Carrell RW
Published: November 2022

Fractionated plasma alpha1-antitrypsin is widely-used as replacement therapy in patients with Z alpha1-antitrypsin deficiency-related emphysema. We have recently shown that purified antitrypsin may be induced to adopt an inactive latent conformation by heating at high temperatures in stabilizing concentrations of sodium citrate. Such a conformation was predicted to be present in commercial preparations of antitrypsin, as these require heating under similar conditions for viral inactivation. Native antitrypsin was purified from plasma, and commercial antitrypsin (Prolastin) was obtained from Bayer Corporation. Western blot analysis of transverse urea gradient (TUG) gels showed that commercial antitrypsin migrated as two bands: one with an unfolding profile of native antitrypsin and the second with a profile of latent antitrypsin. A latent fraction, comprising approximately 8% of the total antitrypsin, was separated from the native antitrypsin in Prolastin by anion exchange chromatography. The specific activity of this latent form against bovine alpha-chymotrypsin increased from 1 to 2% to 50% over 3 h after refolding from 6 M guanidine hydrochloride. These data show that commercial antitrypsin contains a latent component. The significance of this conformation in vivo is unknown, although Prolastin has shown few adverse side-effects in prolonged clinical usage.
Spontaneous haemothorax caused by costal exostosis
Authors: Uchida K , Kurihara Y , Sekiguchi S , Doi Y , Matsuda K , Miyanaga M , Ikeda Y
Published: November 2022

We report a case of spontaneous haemothorax in a 19 year old boy with an exostosis of the left second rib. It may have been caused by nontraumatic rupture of markedly dilated pleural vessels, as a result of long-standing friction between the exostosis and the pleura. This is the first report of spontaneous haemothorax, without penetrative injury to the pleura or the diaphragm, in a patient with hereditary multiple exostosis.
An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD)
Authors: Boyd G , Morice AH , Pounsford JC , Siebert M , Peslis N , Crawford C
Published: November 2022

The objectives of this study were to compare the efficacy and safety of salmeterol xinafoate (50 and 100 microg b.i.d.) with that of placebo, when added to existing therapy, in the treatment of patients with chronic obstructive pulmonary disease (COPD). Six hundred and seventy four patients were randomized to receive either salmeterol 50 microg b.i.d., salmeterol 100 microg b.i.d., or placebo treatment for a period of 16 weeks. The results showed a significant improvement in daily symptom scores noted for patients taking either 50 microg (p=0.043) or 100 microg b.i.d. salmeterol (p=0.01) compared with placebo, with a corresponding decrease in additional daytime salbutamol requirements for both salmeterol groups. The same pattern was reflected for night-time symptoms and additional salbutamol use. During treatment, forced expiratory volume in one second (FEV1) measurements improved significantly in each salmeterol group, with up to a 7% improvement observed at the end of the study. Although no difference was observed between treatment groups for the distance walked in 6 min, patients treated with salmeterol 50 microg b.i.d. were significantly less breathless than those treated with placebo after their 6 min walk, after 8 weeks (p=0.024) and 16 weeks (p=0.004) of therapy. Adverse events were similar in all three groups except for tremor, which was significantly higher in the 100 microg b.i.d. salmeterol group (p=0.005) compared both with 50 microg b.i.d. salmeterol and placebo. Salmeterol offered further positive improvement to the effect of therapy in patients with chronic obstructive pulmonary disease when added to their existing regimens. This clinical improvement was similar both with 50 and 100 microg b.i.d. dosage, although the group receiving 50 microg b.i.d. tolerated the drug better than those receiving 100 microg b.i.d. salmeterol.
The effect of nedocromil sodium on human airway epithelial cell-induced eosinophil chemotaxis and adherence to human endothelial cell in vitro
Authors: Abdelaziz MM , Devalia JL , Khair OA , Rusznak C , Calderon M , Sapsford RJ , Bayram H , Davies RJ
Published: November 2022

Although some studies have shown that long-term treatment of asthmatics with nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and lung function, the mechanisms underlying its effects are not well understood. We have investigated the effect of nedocromil sodium on eosinophil chemotaxis, eosinophil adherence to human endothelial cells and release of soluble intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by conditioned medium collected from cultured human bronchial epithelial cells. Conditioned medium significantly increased eosinophil chemotaxis from a baseline median value of 2.1 (range 1.9-4.5) cells-high power field(-1) (HPF) to 10.5 (range 7.8-12.3) cells-HPF(-1) (p<0.05). Similarly, conditioned medium significantly increased eosinophil adherence to endothelial cells from a baseline value of 9 (range 8-12)% to 23 (range 21-30)% (p<0.05). Nedocromil sodium, at 10(-5) M concentration, significantly attenuated the eosinophil chemotaxis and adherence induced by conditioned medium. Conditioned medium also significantly increased the release of sICAM-1 from endothelial cells, from a baseline value of 11.5 (range 8.1-15.4) pg x microg(-1) protein to 67.6 (range 55.6-73.5) pg x microg(-1) protein (p<0.05). This was significantly attenuated by anti-tumour necrosis factor-alpha (TNF-alpha), anti-interleukin-1beta (IL-1beta) and 10(-5) M nedocromil sodium. These findings suggest that human bronchial epithelial cell-derived mediators may potentiate eosinophil activity, and that this can be modulated by nedocromil sodium, suggesting a possible mechanism underlying its anti-inflammatory effect.
Lung function and airway responsiveness in children and adolescents after hyaline membrane disease: a matched cohort study
Authors: Cano A , Payo F
Published: November 2022

Some investigators consider prematurity to be responsible for the lung function abnormalities found in prematurely born children and adolescents who had neonatal respiratory diseases. This study attempts to measure the effect of neonatal respiratory disease on lung function during school age and adolescence, by controlling the confounding effect due to prematurity. Lung volumes, airway resistance and specific airway conductance measured by plethysmography, maximum expiratory flow-volume curves, pulmonary diffusion of carbon monoxide, and the airway responsiveness to a challenge with methacholine, were determined in a cohort of children aged 8-14 yrs, who had suffered from hyaline membrane disease but who did not develop bronchopulmonary dysplasia. The values obtained were compared with those of children without hyaline membrane disease, not ventilated for other causes, and matched for gestational age, sex and age. Thirty six pairs of children were enrolled, of which 26 participated in the methacholine test. Compared to their paired controls, children with hyaline membrane disease had a significantly lower forced expiratory volume in one second (FEV1), forced mid-expiratory flow (FEF25-75), and maximal expiratory flow when 75, 50 and 25% of the forced vital capacity remained in the lung (MEF75, MEF50 and MEF25, respectively), and a significantly higher airway resistance (Raw). The effect was less in children born more prematurely, who showed less difference in FEF25-75, MEF75 and MEF25. The duration of treatment with steroids in the neonatal period was associated with a reduction in the differences in FEV1, MEF25 and Raw. Independent of prematurity, hyaline membrane disease and its treatment is associated with alterations in long-term lung function, even in children who do not develop bronchopulmonary dysplasia. The effect can be less in more premature children, and neonatal steroids can have a long-term preventive effect.
Ureaplasma urealyticum colonization, prematurity and bronchopulmonary dysplasia
Authors: van Waarde WM , Brus F , Okken A , Kimpen JL
Published: November 2022

The aim of the present study was to determine the association between the presence of Ureaplasma urealyticum in endotracheal aspirates and bronchopulmonary dysplasia (BPD). In addition, a review of similar studies from the English literature is presented. During the period February 1990 until March 1991, 108 mechanically-ventilated infants were included in a prospective study. Endotracheal aspirates were cultured for U. urealyticum. Birth weight, gestational age and development of BPD was recorded. Cultures were positive in 23 infants, resulting in a 21% colonization. The infants with positive cultures had a significantly lower gestational age (mean 28.9 vs 31.5 weeks; range 25-40 vs 25-42 weeks; p=0.0014). A positive U. urealyticum culture was not associated with a low birth weight (mean 1,390 vs 1,690 g; range 675-4,090 vs 700-3,600 g; p=0.0712). A positive U. urealyticum culture was significantly associated with BPD (p=0.0373). However, after correction for gestational age by logistic regression analysis, BPD failed to correlate with the presence of positive U. urealyticum cultures. A MEDLINE search of the English language literature was performed to identify all studies having the association of U. urealyticum colonization and BPD. Fourteen controlled studies were found. Five studies found no significant association between U. urealyticum colonization and BPD. In two studies, after correction for gestational age, the association between U. urealyticum colonization and BPD did not remain significant. In five studies with a significant association between U. urealyticum colonization and BPD, no correction for gestational age had taken place. In conclusion, U. urealyticum colonization is not associated with the development of bronchopulmonary dysplasia. U. urealyticum is often associated with gestational age and/or low birth weight; to investigate the association between U. urealyticum and bronchopulmonary dysplasia correction for both parameters should be made.
Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during mechanical ventilation
Authors: Harvey CJ , O'Doherty MJ , Page CJ , Thomas SH , Nunan TO , Treacher DF
Published: November 2022

Increased delivery of aerosol to a model lung (attached to a mechanical ventilator) has been demonstrated with an ultrasonic nebulizer as compared to a jet nebulizer. This study examined whether the increased aerosol deposition with an ultrasonic nebulizer could also be demonstrated in vivo. Seven patients (6 male and 1 female) were studied during mechanical ventilalion (Siemens Servo 900C, Middlesex, UK) after open heart surgery. Two studies were performed in each patient. In the first study, aerosol was delivered via a Siemens Servo 945 nebulizer system (high setting) driving a System 22 Acorn jet nebulizer (Medic-Aid, Sussex, UK) containing 3 mL (99m)technetium-labelled human serum albumin (99mTc-HSA) (50 microg; activity 74 MBq). In the second study, a DP100 ultrasonic nebulizer (DP Medical, Meylan, France) containing 12 mL 99mTc-HSA (50 microg; activity 185 MBq) was used. Pulmonary deposition was quantified using a gamma camera. The humidification of the circuit and the ventilator settings were kept constant according to the patient's clinical requirements. The total lung aerosol deposition (mean+/-SD), as a percentage of initial nebulizer activity, was greater using the ultrasonic nebulizer than using the jet nebulizer (53+/-1.4 vs 2.3+/-0.9%; p<0.002). The ultrasonic nebulizer was also associated with a reduction in the time required to complete nebulization (9 vs 21 min, respectively) (p<0.0001). Use of the DP100 ultrasonic nebulizer more than doubled lung deposition compared with the System 22 jet nebulizers in mechanically-ventilated patients. Their efficiency, speed of drug delivery, and compatibility with mechanical ventilator circuits make ultrasonic nebulizers potentially attractive for use during mechanical ventilation.
Impact of sleep in respiratory failure
Authors: McNicholas WT
Published: November 2022

Sleep has a physiological influence on respiration, which can have major adverse effects on gas exchange in patients with respiratory insufficiency. These effects relate largely to a reduction in various stimulant inputs to the brainstem respiratory centre. Conditions that may be associated with sleep-related respiratory insufficiency range from pulmonary disorders (such as chronic obstructive pulmonary disease (COPD)), to central respiratory insufficiency (such as central alveolar hypoventilation), neurological and neuromuscular disorders (such as polio and muscular dystrophy), and thoracic cage disorders (such as kyphoscoliosis). All these conditions have in common the finding of hypoxaemia and hypercapnia, which become more pronounced during sleep. The relative hypoventilation, which is common to each condition, is due to varying combinations of an inadequate respiratory drive and an increase in the work of breathing. Management of respiratory insufficiency during sleep should be directed first at optimizing the underlying disorder, then at correcting hypoxaemia with controlled low-flow supplemental oxygen. Pharmacological therapy may be effective in some instances, but the choice of agent varies with the underlying disorder. Assisted ventilation is an important part of the management of advanced cases, and the recent development of intermittent positive pressure ventilation by nasal mask (NIPPV) has been an important advance in this area. Use of NIPPV during the night is associated with beneficial effects during the day, particularly improved awake gas exchange and respiratory muscle strength, in addition to less dyspnoea and improved quality of life. Electrophrenic pacing of the diaphragm is helpful in highly selected cases, particularly patients with central respiratory insufficiency and high quadriplegia, but is frequently complicated by the development of obstructive sleep apnoea.
Hyperinflation and respiratory muscle interaction
Authors: Decramer M
Published: November 2022

Hyperinflation clearly affects respiratory muscle interaction. It commonly increases the rib cage contribution to chest wall motion, whilst it reduces the abdominal contribution. This change is thought to result from the fact that hyperinflation severely reduces the mechanical advantage of the diaphragm, whilst it affects the mechanical advantage of the neck and rib cage muscles to a lesser extent. The mechanical disadvantage in the diaphragm induced by hyperinflation is presumably primarily the result of the length changes undergone by the diaphragm in acute hyperinflation. Changes in diaphragmatic geometry are generally considered to be less important in the reduction of the diaphragm's force-generating capacity. Further factors contributing to the mechanical disadvantage in the diaphragm include a reduction in the appositional component of diaphragmatic action (through reduction in the zone of apposition), and a reduction in the insertional component (through a shift in the alignment of the diaphragmatic fibres from axial to radial). In chronic hyperinflation, the diaphragm adapts to the chronically hyperinflated state. This adaptation to chronic foreshortening is similar to the adaptation occurring in the skeletal muscle. It is caused by a dropout of sarcomeres in series along the muscle fibres. It restores the force-generating capacity of the muscle, in part, but it reduces the capacity of the muscle to undergo length changes. The mechanical advantage of the parasternal intercostals and the scalenes is possibly less affected, because the length changes undergone by these muscles during hyperinflation are smaller. The factors determining the mechanical advantage of the parasternal intercostals are complex. Variables related to the mechanical advantage of the parasternal intercostals include: length changes; changes in angle between the parasternal intercostals and the sternum and between rib and sternum; and changes in mechanical arrangement among different parasternals. At present, it is difficult to develop an integrated view of these factors and of their change with hyperinflation. Finally, hyperinflation commonly results in recruitment of expiratory muscles. The functional significance of this expiratory muscle recruitment in patients is still debated.
Intravascular lymphomatosis diagnosed by transbronchial lung biopsy
Authors: Takamura K , Nasuhara Y , Mishina T , Matsuda T , Nishimura M , Kawakami Y , Fujita M , Mikuni C , Yamashiro K
Published: November 2022

Intravascular lymphomatosis is a rare lymphoma presenting a variety of symptoms due to proliferation of tumour cells within blood vessels in the brain, the skin and other organs. This disease is generally considered to be highly malignant, but to be relatively susceptible to combined chemotherapy, when diagnosed in the early stage. We describe a case of intravascular lymphomatosis, presenting with diffuse interstitial shadows on chest radiographic image, which could be diagnosed by transbronchial lung biopsy. The patient showed a good response to combined chemotherapy. We propose that transbronchial lung biopsy is a useful procedure for the diagnosis of intravascular lymphomatosis.
Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia
Authors: Maus U , Rosseau S , Knies U , Seeger W , Lohmeyer J
Published: November 2022

The aim of the present study was to further characterize the role of alveolar macrophages (AM) in acute human lung inflammation by evaluating their capacity to produce pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Patients with severe community-acquired pneumonia (CAP; n=12) and healthy volunteers (n=10) underwent bronchoalveolar lavage (BAL). AM were separated to high purity (>96%) using fluorescence-activated cell sorting. We determined the TNF-alpha, IL-6 and IL-8 cytokine gene expression in AM ex vivo using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Moreover, we measured in vitro unstimulated, lipopolysaccharide (LPS)- and LPS/interferon-gamma inducible TNF-alpha, IL-6 and IL-8 cytokine release and evaluated samples of BAL fluids for the same pro-inflammatory cytokines using an enzyme-linked immunosorbent assay (ELISA). We found increased TNF-alpha, IL-6 and IL-8 messenger ribonucleic acid (mRNA) levels in AM from CAP patients that were significantly elevated only for IL-8. When challenged with endotoxin in vitro, AM obtained from CAP patients showed a strongly reduced potential to release TNF-alpha and IL-6 compared to healthy controls, whereas IL-8 secretion did not differ significantly between groups. Moreover, stimulation of AM from CAP patients with LPS plus IFN-gamma augmented TNF-alpha and IL-6 cytokine release to near normal levels. Interestingly, no TNF-alpha protein was measured in BAL samples from CAP patients, whereas IL-6 and IL-8 protein levels were found to be significantly increased. Together, highly purified alveolar macrophages from community-acquired pneumonia patients show relatively low ex vivo tumour necrosis factor-alpha and interleukin-6 but not interleukin-8 messenger ribonucleic acid levels that are associated with a decreased pro-inflammatory cytokine release in vitro which, however, can be restored by concurrent interferon-gamma stimulation.
Surfactant changes during experimental pneumocystosis are related to Pneumocystis development
Authors: Aliouat EM , Escamilla R , Cariven C , Vieu C , Mullet C , Dei-Cas E , Prevost MC
Published: November 2022

Pneumocystosis-related surfactant changes have been reported in both humans and corticosteroid-treated experimental hosts. As corticosteroids induce an increase in pulmonary surfactant, some findings could be considered as controversial. The aim of this study was to investigate whether the surfactant composition changes during experimental pneumocystosis were related to the Pneumocystis development. In this work two corticosteroid-untreated animal models were used: rabbits, which develop spontaneous pneumocystosis at weaning; and severe combined immunodeficiency mice, which were intranasally inoculated with Pneumocystis carinii. Surfactant phospholipid and protein content was explored by bronchoalveolar lavage. The in vitro effect of surfactant on P. carinii growth was also explored. In the two models, the surfactant phospholipid/protein ratio was significantly increased, whereas parasite rates were low. This ratio decreases with the slope increase of the parasite growth curve. These early surfactant changes suggested that Pneumocystis proliferation requires alveolar lining fluid changes, and that normal surfactant is not suitable for parasite development. In this way, in vitro experiments presented here have revealed an inhibitory effect of synthetic or seminatural surfactants on the P. carinii growth. Further studies are needed to determine how Pneumocystis induces the reported early modifications of the surfactant, and why the parasite development is inhibited by pulmonary surfactant.
Effects of corticosteroids on epithelial structure and smooth muscle function of rat trachea
Authors: Pavlovic D , Viires N , Zedda C , Fournier M , Aubier M
Published: November 2022

Corticosteroids, efficient drugs for the treatment of severe asthma, may have numerous side effects. We investigated the effects of 7 days of treatment with triamcinolone (1.2 mg x kg(-1) x day(-1)) on the epithelial structure, tracheal smooth muscle cross-sectional area and contractility in the rat. The corticosteroid-injected rats were compared to pair-fed, and pair-weighed animals. Histological studies were performed on transverse sections of glutaraldehyde-fixed tracheal blocks embedded in plastic. In the preparations taken from corticosteroid-injected, pair-fed and pair-weighed animals, pharmacological stimulation with single (10(-3) M) or cumulative (10(-8)-10(-3) M) concentrations of carbachol (in corticosteroid-injected and pair-fed animals), either inside (In) or outside (Out) of the tracheal lumen, was performed and contractions of the tracheal smooth muscle were recorded. We found that triamcinolone administration: 1) reduced the number of epithelial cells and the tracheal smooth muscle cross-sectional area; 2) induced a decrease in maximal tension (Tmax (g); Out: 2.42+/-0.17, 1.03+/-0.1 in pair-fed and corticosteroid-injected, respectively; In: 2.55+/-0.16, 1.1+/-0.16, respectively) without affecting the sensitivity of the tracheal smooth muscle; and 3) reduced the time required to reach 50% Tmax in carbachol (In) preparations. We conclude that the observed changes resulted from atrophy of tracheal smooth muscle induced by undernutrition and atrophy of tracheal smooth muscle and tracheal epithelium induced by corticosteroid treatment.
Long- and short-acting beta2 adrenoceptor agonists: interactions in human contracted bronchi
Authors: Molimard M , Naline E , Zhang Y , Le Gros V , Begaud B , Advenier C
Published: November 2022

The aim of this study was to systematically compare the interaction of the long-acting beta2-adrenoceptor agonists formoterol and salmeterol with short-acting beta2-adrenoceptor agonists in contracted human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Formoterol or salmeterol at concentrations inducing up to 92 and 94% of their maximal relaxant effect, respectively, were added to bronchial rings contracted with carbachol (10(-6) M). After a time period of 30 min, concentration-response curves for the short-acting beta2-adrenoceptor agonists, salbutamol, terbutaline, isoprenaline and fenoterol were recorded. Administration of equieffective concentrations of salmeterol and formoterol, resulted in only salmeterol inducing a shift to the right of isoprenaline, terbutaline, fenoterol and salbutamol concentration-response curves. The rank order of shift was salbutamol > fenoterol > terbutaline > isoprenaline. Formoterol, up to concentrations of 3x10(-9) M induced submaximal relaxation resulting in no shift in short-acting beta2-adrenoceptor agonist concentration-response curves. Salmeterol but not formoterol appears to antagonize the relaxation of human contracted bronchi induced by short-acting beta2-agonists. These results obtained in vitro cannot be translated in clinical terms. This study, however, highlights the need for clinical studies on the interaction of long-acting and short-acting beta2-adrenoceptor agonists in acute severe asthma.
Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma
Authors: Hancox RJ , Sears MR , Taylor DR
Published: November 2022

Polymorphisms affecting amino acids 16 and 27 of the beta2-adrenoceptor alter receptor regulation in vitro. Whether these polymorphisms alter the response to beta2-agonist therapy in asthma is unknown. In a previous study of 64 asthmatics, most experienced a deterioration in asthma control during regular inhaled beta2-agonist (fenoterol) treatment, while a minority improved. We have determined the beta2-adrenoceptor genotypes in these subjects, to establish whether changes in asthma control during the earlier study were influenced by beta2-adrenoceptor polymorphism. The genotypes coding for amino acids 16 and 27 were identified in 60 subjects using allele-specific polymerase chain reaction. The effects of regular beta2-agonist treatment on asthma control were compared between genotypes. There was no association between genotype and change in overall asthma control during regular beta2-agonist treatment. Only two of 10 markers of asthma control showed changes that were significantly associated with genotype: subjects homozygous for glycine at position 16 had no increase in bronchial responsiveness to methacholine during regular treatment; subjects homozygous for glutamic acid at position 27 had no increase in evening peak expiratory flow rates during regular treatment. These differences are the opposite of those that would have been predicted by the results of in vitro studies. In these subjects, the deleterious response to regular inhaled beta2-agonist treatment was not related to beta2-receptor polymorphism.
The effects of static charge in spacer devices on glucocorticosteroid aerosol deposition in asthmatic patients
Authors: Kenyon CJ , Thorsson L , Borgstrom L , Newman SP
Published: November 2022

Electrostatic charge in plastic spacer devices has been shown in vitro to reduce delivery of asthma medications intended for inhalation, but the effect of static charge on in vivo drug deposition is unknown. A six-way randomized crossover study was conducted in 10 mild asthmatic patients. Two plastic spacers (Nebuhaler and Volumatic) and one metal spacer (Nebuchamber) were tested. The spacers were used either "primed" or "unprimed". Priming was performed by firing 20 doses of placebo aerosol into a new spacer, hence coating the inner surface with surfactant and minimizing static charge. Unprimed spacers were new and were not treated. Pressurized aerosol canisters delivering budesonide (200 microg Pulmicort) were radiolabelled with the radionuclide 99mTc and lung deposition was measured by gamma scintigraphy. The radiolabel was shown to be a valid marker for the drug substance prior to the clinical phase of the study. Priming significantly increased mean whole lung deposition following inhalation from plastic spacers (Nebuhaler primed 37.7% and unprimed 26.7%, p=0.01; Volumatic primed 32.0% and unprimed 22.1%, p=0.02). Priming had no effect on the mean whole lung deposition following inhalation from the Nebuchamber (primed 33.5% and unprimed 32.9%). Lung deposition in vivo from plastic spacer devices will vary according to the electrostatic charge on the spacer walls. Priming reduces retention of drug on plastic spacer devices and increases lung deposition. Metal spacers are not susceptible to static charge, which should result in more predictable lung deposition.
Effects of a 5-lipoxygenase inhibitor, ABT-761, on exercise-induced bronchoconstriction and urinary LTE4 in asthmatic patients
Authors: Lehnigk B , Rabe KF , Dent G , Herst RS , Carpentier PJ , Magnussen H
Published: November 2022

The novel 5-lipoxygenase (5-LO) inhibitor, ABT-761, was investigated for its effect on exercise-induced bronchoconstriction in asthmatic subjects. The relationship between 5-LO inhibition and effects on the response of the airways to exercise was examined. In a double-blind, randomized, crossover clinical trial, 10 patients with mild to moderate persistent asthma (who exhibited a fall in forced expiratory volume in one second (FEV1) > or = 20% following standardized exercise challenge) received 200 mg ABT-761 or matched placebo, orally, 5 h prior to exercise on two study days, 7-10 days apart. Lung function, urinary leukotriene E4 (LTE4) and ex vivo calcium ionophore-stimulated LTB4 release in whole blood were measured prior to dosing, prior to exercise and at various time points up to 4 h post-exercise. The mean (SD) maximal percentage fall in FEV1 after exercise was 27.1 (12)% on placebo and 19.9 (10)% on ABT-761 days, respectively (p<0.05). Post-exercise fall in FEV1 was significantly attenuated at 5, 10, 15 and 30 min after exercise and the mean area under curve, representing the overall effect of exercise from 0-45 min post-challenge, was also significantly attenuated by ABT-761 (p<0.001). Ex vivo LTB4 release was inhibited by more than 80% throughout the 4 h post-exercise period, indicating that 5-LO was extensively inhibited at all time points. Urinary LTE4 in the post-exercise period was significantly lower after ABT-761 day than after placebo (40.1 (17.6) versus 89.8 (58.2) pg x mg creatinine(-1); p<0.05). Inhibition of LTB4 release in ABT-761-treated patients correlated positively with the attenuation of post-exercise FEV1 decline (r=0.711; p<0.05). We conclude that ABT-761 is effective in suppressing exercise-induced bronchoconstriction and that this protection is related quantitatively to the degree of 5-lipoxygenase inhibition.
Bronchopulmonary disease in Iranian housewives chronically exposed to indoor smoke
Authors: Amoli K
Published: November 2022

Tobacco smoking is recognized as the main cause of chronic bronchitis followed by occupational exposure to dust, fumes and gases. Indoor inhalation of smoke is being investigated increasingly but mainly the acute morbidity has been described while the late features and complications which may lead to respiratory disability are less well known. Among the 388 female patients who were referred to the main Bronchoscopy Unit of Tehran University of Medical Sciences between 1986 and 1995, 10 nonsmoking elderly housewives were found with chronic bronchopulmonary lesions characterized by widespread mucosal swelling and anthracotic plaques of the airways. Enquiry into their past history revealed massive exposure to smoke over many years whilst baking household rustic bread inside dwellings. No other source of air pollution was detected. The main clinicopathological features were respiratory disability due to chronic bronchitis with intracellular as well as extracellular black particles. As similar cases may present to medical practitioners even in affluent societies as a result of increasing amounts of immigrants from developing countries, recognition of these patients is important to avoid irrelevant diagnoses and unnecessary interventions.
Increased sensitivity of the cough reflex in progressive systemic sclerosis patients with interstitial lung disease
Authors: Lalloo UG , Lim S , DuBois R , Barnes PJ , Chung KF
Published: November 2022

Cough is a common presenting symptom of interstitial lung disease (ILD). The aim of this study was to examine the cough reflex in patients with progressive systemic sclerosis (PSS), with and without associated ILD. The cough reflex to inhalation of chloride deficient solutions and capsaicin was determined in patients with PSS with associated ILD (n=12), compared to patients with PSS without ILD (n=12). In addition, patients with a chronic dry cough (n=12) and healthy subjects (n=10) without cough were studied. Cough responses to inhalation of isotonic solutions containing 150, 75, 37.5 and 0 mM Cl- ions and of capsaicin (0.9-500 mM) were measured. PSS patients with ILD reported a significantly higher cough score than PSS patients without ILD (p<0.03). ILD patients coughed more than those without ILD to Cl- of 37.5 and 0 mM (19.1+/-5.0 vs 6.2+/-1.9 coughs x min(-1) (p<0.03), and 29.2+/-5.0 vs 14.1/-4.1 coughs x min(-1) (p<0.04), respectively). The log concentration of capsaicin causing two or five coughs was lower in PSS with ILD compared to PSS without ILD (0.74+/-0.15 mM vs 2.12+/-0.26 mM; p<0.002). Patients with chronic dry cough had a similar degree of response to low-chloride and capsaicin solutions as patients with PSS and ILD, whilst healthy controls had a similar degrees of response to PSS patients. There is an increased cough reflex in patients with interstitial lung disease, which may represent sensitization of airway sensory nerves. This may be the basis for the chronic dry cough in patients with interstitial lung disease.
Risk of serious COVID-19 outcomes among adults and children with moderate-to-severe asthma: a systematic review and meta-analysis
Authors: Lee Bohee , Lewis Grace , Agyei-Manu Eldad , Atkins Nadege , Bhattacharyya Urmila , Dozier Marshall , Rostron Jasmin , Sheikh Aziz , McQuillan Ruth , Theodoratou Evropi
Published: November 2022

Background

The Joint Committee on Vaccination and Immunisation in the United Kingdom requested an evidence synthesis to investigate the relationship between asthma and coronavirus disease 2019 (COVID-19) outcomes.

Objective

We conducted a systematic review and meta-analysis to summarise evidence on the risk of severe COVID-19 outcomes in people with uncontrolled asthma or markers of asthma severity.

Methods

High-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) were used as markers of asthma severity, following international or national asthma guidelines. Risk of bias was assessed using Joanna Briggs Institute tools. Adjusted point estimates were extracted for random-effects meta-analyses and subgroup analyses.

Results

After screening, 12 studies (11 in adults and one in children) met the eligibility criteria. Adults using high-dose ICS or OCS had a pooled adjusted hazard ratio (aHR) of 1.33 (95% CI 1.06–1.67, I2=0%) for hospitalisation and an aHR of 1.22 (95% CI 0.90–1.65, I2=70%) for mortality for COVID-19. We found insufficient evidence for associations between markers on COVID-19 mortality in the subgroup analyses.

Conclusions

Adults with severe asthma are at increased risk of COVID-19 hospitalisation compared to nonusers. Our analysis highlighted the dearth of studies in children with asthma investigating serious COVID-19 outcomes.
Effect of tracheal tube cuff inflation with alkalinized lidocaine versus air on hemodynamic responses during extubation and post-operative airway morbidities in children: prospective observational cohort study, Ethiopia
Authors: Assefa Biniam , Samuel Hirbo , Fentie Fissiha , Daniel Tenbite , Hika Assefa , Aberra Bacha , Alemu Belete
Published: November 2022

Background

Endotracheal tube with an inflated cuff was used to manage and maintain the airway during general anesthesia in children. When the lateral pressure exerted by an inflated Endotracheal tube cuff on tracheal mucosa exceeds capillary perfusion pressure, patients may complain of cough, sore throat, and hoarseness in the postoperative period. This study aimed to assess the effect of a tracheal tube cuff filled with alkalinized lidocaine versus air on hemodynamic parameter changes during extubation and post-operative airway morbidity in children.

Methods

Institutional based observational prospective cohort study was conducted among 56 elective children; aged 3–13 years, who underwent operation under general anesthesia with cuffed endotracheal intubation for greater than one hour by grouping into the air (group1) and alkalinized Lidocaine (group2) at Tikur Anbessa specialized Hospital. Hemodynamic parameters (Heart rate and Blood pressure) and other variables were measured starting from 5 min before extubation to 24th hours after extubation of the endotracheal tube. A Comparison of numerical variables between study group was done with an independent t-test. Data were expressed in terms of mean ± standard deviation. Categorical data were assessed by Chi-square tests.

Results

Postoperative Sore throat was lower in alkalinized lidocaine group compared to the air group. The mean heart rate at five minutes after extubation was significantly lower in alkalinized lidocaine group (107.29 ± 6.457 beat per minute (bpm)) compared to the air group (122.04 ± 8.809 bpm), with P ≤ 0.001. Systolic blood pressure was also significantly lower in alkalinized lidocaine group (99.64 ± 8.434 millimeters of mercury (mmHg)) compared to the air group (108.21 ± 11.902 mmHg), p = 0.016 at five minutes after extubation.

Conclusion

Alkalinized lidocaine inflated tracheal tubes have shown improved hemodynamic and laryngotracheal morbidities in children.
Zero-augmented beta-prime model for multilevel semi-continuous data: a Bayesian inference
Authors: Kamyari Naser , Soltanian Ali Reza , Mahjub Hossein , Moghimbeigi Abbas , Seyedtabib Maryam
Published: November 2022

Semi-continuous data characterized by an excessive proportion of zeros and right-skewed continuous positive values appear frequently in medical research. One example would be the pharmaceutical expenditure (PE) data for which a substantial proportion of subjects investigated may report zero. Two-part mixed-effects models have been developed to analyse clustered measures of semi-continuous data from multilevel studies. In this study, we propose a new flexible two-part mixed-effects model with skew distributions for nested semi-continuous cost data under the framework of a Bayesian approach. The proposed model specification consists of two mixed-effects models linked by the correlated random effects: Part I) a model on the occurrence of positive values using a generalized logistic mixed model; and Part II) a model on the magnitude of positive values using a linear mixed model where the model errors follow skew distributions including beta-prime (BP). The proposed method is illustrated with pharmaceutical expenditure data from a multilevel observational study and the analytic results are reported by comparing potential models under different skew distributions. Simulation studies are conducted to assess the performance of the proposed model. The DIC3, LPML, WAIC, and LOO as the Bayesian model selection criteria and measures of divergence used to compare the models.