bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupational asthma due to zinc
Authors: Malo JL , Cartier A , Dolovich J
Published: November 2022

We describe a subject who developed asthma symptoms 2 yrs after being employed at a plant where metals were galvanized in heated zinc. The subject was not atopic. Baseline spirometry was normal three months after he left work but there was mild bronchial hyperresponsiveness to methacholine. Monitoring of forced expiratory volume in one second (FEV1) during a day at work showed a maximum fall in FEV1 of 24% at the end of the day and an increase in bronchial responsiveness on the following day. Environmental monitoring revealed that zinc and iron were present in the working environment at concentrations that were lower than the "threshold limit value-short term exposure level" (TLV-STEL) standards. Positive immediate skin tests to zinc sulphate at concentrations of 1 and 10 mg.ml-1 were obtained, although no specific immunoglobulin E (IgE) antibodies to zinc could be found. Skin tests with copper, chromium and cobalt were negative. Specific inhalation challenges were performed, having the subject inhale a solution of zinc sulphate at a 10 mg.ml-1 concentration for 6 min. An immediate reaction was elicited (maximum fall in FEV1 of 23%). We conclude that zinc can cause occupational asthma.
Density of phenotypic markers on BAL T-lymphocytes in hypersensitivity pneumonitis, pulmonary sarcoidosis and bronchiolitis obliterans with organizing pneumonia
Authors: Satake N , Nagai S , Kawatani A , Kaneshima H , Tanaka S , Takeuchi M , Izumi T
Published: November 2022

In vitro studies have shown that the density of surface antigens reflects the degree of activation of T-cells. We therefore studied the density of surface antigens on T-cells from bronchoalveolar lavage fluid (BALF) and blood in patients with sarcoidosis, hypersensitivity pneumonitis (HP) and bronchiolitis obliterans with organizing pneumonia (BOOP). BALF cells were stained with anti-CD3, anti-CD4, anti-CD8 and anti-human leucocyte antigen-DR(HLA-DR) monoclonal antibodies, and were analysed by cytoflowmetry. The density was evaluated by measuring the Mean Channel fluorescence intensity of the stained cells. The results demonstrated a significant increase in the CD3 density in patients with hypersensitivity pneumonitis (108.2 +/- 20.2 MC), compared with those with pulmonary sarcoidosis (51.2 +/- 12.6), BOOP (74.5 +/- 29.3), and healthy controls (57.1 +/- 11.5). Similar results were obtained for the CD4 and CD8 density in patients with HP. Although the number of HLA-DR positive cells was increased, the density was lower in patients with sarcoidosis (57.4 +/- 11.6) and hypersensitivity pneumonitis (57.4 +/- 14.8), than in healthy controls (72.2 +/- 15.1). Comparable changes were not observed in the peripheral blood. These results suggest that T-cell activation in hypersensitivity pneumonitis may be associated with an increase in the CD3, CD4, and CD8 density on BALF T-cells.
Respiration after phrenicotomy and hydrocortisone treatment in anaesthetized rats
Authors: Nachazel J , Palecek F
Published: November 2022

The study was designed to determine the extent to which respiratory muscle wasting, resulting from corticosteroid-induced atrophy, may affect respiration in normal rats and in rats with denervated diaphragm. Twenty four male Wistar rats were divided into four groups: 1) controls with sham operation (SX) and vehicle injections: 2) SX with eight hydrocortisone (HC) injections (60 mg.kg-1.day-1 i.m.); 3) phrenicotomized (PX), injected with vehicle; 4) PX and HC-treated. HC treatment was started on the thirteenth day after surgery. Under urethane anaesthesia, tidal volume, respiratory rate, arterial carbon dioxide tension (PaCO2) and occlusion pressure were measured at rest and after 5 min of stimulated-breathing induced by added dead space 22nd day after surgery. All HC-treated animals decreased body weight by 32% compared to untreated rats. The diaphragm weight was reduced in PX rats by 29%, and after HC by 44%, while in PX rats with HC treatment diaphragm weight decreased by only 21%. PX rats (HC-untreated) had the lowest minute ventilation and occlusion pressure. There was no difference in ventilation between control and both HC-treated groups at rest. However, ventilation in PX and HC-treated rats did not increase upon stimulation, and the occlusion pressure increased significantly only in the HC-untreated animals. We conclude that in the rat, HC treatment did not affect resting ventilation, but it impaired ventilation performance, during increased demand, in animals handicapped by diaphragm denervation.
Kinins and respiratory tract diseases
Authors: Trifilieff A , Da Silva A , Gies JP
Published: November 2022

Bradykinin and related kinins are peptidic hormones, formed in tissues and fluids during inflammation. Various functional sites have been proposed as mediators of the biological effects of kinins, including the B1, B2 and B3 receptors. The existence of the B1 and the B2 receptor has largely been confirmed, whilst that of the B3 receptor is controversial and needs further confirmation. The role of bradykinin in the pathophysiology of asthma is not well understood, but bradykinin was proposed as a putative mediator of asthma, since asthmatic subjects are hyperresponsive to bradykinin, and since immunoreactive kinins are increased in the bronchoalveolar lavage fluids of asthmatic patients. Kinins could provoke bronchoconstriction by acting directly on smooth muscle and/or indirectly by their inflammatory properties. They may also contribute to the symptomatology of allergic and viral rhinitis, since they are the only mediators detected to date that are generated in nasal secretion during experimental and natural rhinovirus colds. Moreover, they can induce relevant symptoms when applied to airway mucosa. It has also been proposed that coughing during treatment with angiotensin-converting enzyme (ACE) inhibitors is linked to the action of kinins, since ACE is able to degrade kinins, and since the effects of ACE inhibitors are reduced by kinin antagonists. Due to their mitogenic properties, kinins have been proposed to regulate lung carcinoma growth. Their action remains speculative, but some findings are of great interest in order to define their role in these pathologies. Despite many studies in animals and in humans, the mode of action of kinins in airways is still poorly understood.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of five years of nocturnal cuirass-assisted ventilation in chest wall disease
Authors: Jackson M , Kinnear W , King M , Hockley S , Shneerson J
Published: November 2022

We investigated the long-term effectiveness of cuirass-assisted ventilation, and examined whether mortality and morbidity could have been predicted at the time of admittance. Twenty five patients were commenced on nocturnal cuirass-assisted ventilation between 1983 and 1985, 10 with scoliosis or kyphosis, 8 with a thoracoplasty and 7 with neuromuscular disease. Mean pretreatment vital capacity was 30% of predicted, and arterial carbon dioxide tension (Paco2) was 8.2 kPa (62 mmHg). Fifteen patients were alive 5 yrs later. Two had discontinued assisted ventilation, both dying soon afterwards, and three had been changed to intermittent positive pressure ventilation. Survival could not have been predicted from age, severity of disease, lung volumes or arterial blood gases at presentation. Paco2 in the survivors had risen from a mean of 6.1 kPa (46 mmHg) after one year to 6.8 kPa (52 mmHg) after 5 yrs (p < 0.05), but remained significantly less than at presentation. There were no significant change in arterial oxygen tension (Pao2), lung volumes, respiratory muscle strength, haemoglobin, right heart failure, exercise tolerance, mental function and symptom scores after 5 yrs, compared to after 1 yr. The median amount of time spent in hospital declined from 15 days per patient in the first year after initial discharge with cuirass-assisted ventilation, to between 3-5.5 days per patient in subsequent years. We conclude that nocturnal cuirass-assisted ventilation has a role in long-term management of patients with neuromuscular and skeletal chest wall disorders. A randomized comparison with nasal intermittent positive pressure ventilation is now indicated.
Predictive nature of bronchial responsiveness and respiratory symptoms in a one year cohort study of Sydney schoolchildren
Authors: Peat JK , Toelle BG , Salome CM , Woolcock AJ
Published: November 2022

We wanted to examine the predictive nature, over one year, of bronchial hyperresponsiveness (BHR) and recent wheeze (in the previous 12 months), which are the measurements frequently used to classify asthma for epidemiology. A prospective cohort study of 236 children, aged 8-11 yrs, was undertaken, with an initial baseline study, followed by four studies at three monthly intervals over one year. At each study, we measured bronchial responsiveness to histamine by the rapid method, respiratory symptoms by parent questionnaire, and atopy by skin prick tests to common allergens. Airflometer readings, which are closely related to FEV1, were self-recorded. Baseline data were used to classify children into the four categories of "current asthma" (BHR and wheeze), "wheeze only", "BHR only", or "normal". During the year following baseline study, the group initially classified as "wheeze only" had normal Airflometer variability, and 59% had wheeze, and 33% had BHR, which tended to be mild. In the group initially classified as "BHR only", 52% had wheeze with a peak in winter, and 62% had BHR during the following year. This group had more severe bronchial responsiveness and Airflometer variability than the normal and wheeze only groups. The group initially classified as current asthma had a more severe condition, with continued BHR (100%), and wheeze (93%), increased Airflometer variability and more atopy. Thus, the natural history of bronchial responsiveness, respiratory symptoms and allergic history in this group was different from the other three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory function of the rib cage muscles
Authors: Han JN , Gayan-Ramirez G , Dekhuijzen R , Decramer M
Published: November 2022

Elevation of the ribs and expansion of the rib cage result from the co-ordinated action of the rib cage muscles. We wished to review the action and interaction of the rib cage muscles during ventilation. The parasternal intercostal muscles appear to play a predominant role during quiet breathing, both in humans and in anaesthetized dogs. In humans, the parasternal intercostals act in concert with the scalene muscles to expand the upper rib cage, and/or to prevent it from being drawn inward by the action of the diaphragm. The external intercostal muscles are considered to be active mainly during inspiration, and the internal intercostal muscles during expiration. The respiratory activity of the external intercostals is minimal during quiet breathing both in man and in dogs, but increases with increasing ventilation. Inspiratory activity in the external intercostals can be enhanced in anaesthetized animals and humans by inspiratory mechanical loading and by CO2 stimulation, suggesting that the external intercostals may constitute a reserve system, that may be recruited when the desired expansion of the rib cage is increased. The triangularis sterni is an important expiratory muscle during quiet breathing in animals, but it is not active during quiet breathing in man. However, during expiration below functional residual capacity (FRC), and during speech, laughing and coughing, the triangularis sterni is recruited and plays an increasingly important role.
Acute eosinophilic pneumonia in a heroin smoker
Authors: Brander PE , Tukiainen P
Published: November 2022

Inhalation of heroin is known to provoke asthma. We report on the case of a patient who, after repeated inhalation of heroin, presented with decreased lung volume associated with bronchial hyperresponsiveness, diffuse pulmonary infiltrates, and bronchoalveolar lavage fluid eosinophilia. Rapid remission was obtained after heroin abstinence and initiation of corticosteroid treatment.
Respiratory mechanics studied by forced oscillations during artificial ventilation
Authors: Peslin R , Felicio da Silva J , Duvivier C , Chabot F
Published: November 2022

Potential advantages of the forced oscillation technique over other methods for monitoring total respiratory mechanics during artificial ventilation are that it does not require patient relaxation, and that additional information may be derived from the frequency dependence of the real (Re) and imaginary (Im) parts of respiratory impedance. We wanted to assess feasibility and usefulness of the forced oscillation technique in this setting and therefore used the approach in 17 intubated patients, mechanically ventilated for acute respiratory failure. Sinusoidal pressure oscillations at 5, 10 and 20 Hz were applied at the airway opening, using a specially devised loudspeaker-type generator placed in parallel with the ventilator. Real and imaginary parts were corrected for the flow-dependent impedance of the endotracheal tube; they usually exhibited large variations during the respiratory cycle, and were computed separately for the inspiratory and expiratory phases. In many instances the real part was larger during inspiration, probably due to the larger respiratory flow, and decreased with increasing frequency. The imaginary part of respiratory impedance usually increased with increasing frequency during expiration, as expected for a predominately elastic system, but often varied little, or even decreased, with increasing frequency during inspiration. In most patients, the data were inconsistent with the usual resistance-inertance-compliance model. A much better fit was obtained with a model featuring central airways and a peripheral pathway in parallel with bronchial compliance. The results obtained with the latter model suggest that dynamic airway compression occurred during passive expiration in a number of patients. We conclude that the use of forced oscillation is relatively easy to implement during mechanical ventilation, that it allows the study of respiratory mechanics at various points in the respiratory cycle, and may help in detecting expiratory flow limitation.
Different effects of inhaled amiloride and frusemide on airway responsiveness to dry air challenge in asthmatic subjects
Authors: Rodwell LT , Anderson SD , du Toit J , Seale JP
Published: November 2022

Amiloride, a Na+ channel blocker, and frusemide, an inhibitor of the Na+/K+/2Cl- co-transporter on the basolateral surface of airway epithelial cells, have the potential to affect water transport across the airway epithelium. As isocapnic hyperventilation challenge (ISH) with dry air may provoke airway narrowing in asthmatic subjects by dehydrating the airways, inhaled amiloride and frusemide may reduce airway responsiveness by effecting airway hydration. Fifteen asthmatic subjects (6 females, 9 males), who had a fall in forced expiratory volume in one second (FEV1) of 20% after ISH, inhaled amiloride (11 mg), or its vehicle, from a Fisoneb ultrasonic nebulizer, within 10 min before ISH. On a separate day, eight of these subjects inhaled frusemide (38 mg), from the same Fisoneb, 10 min before ISH. After breathing, 30 l at resting ventilation, subjects breathed at 30% of their maximum voluntary ventilation (MVV i.e. predicted FEV1x35), then at 60% MVV, and finally at MVV for 3 or 4 min. FEV1 was measured 1, 3, 5, 7 and 9 min after each period, or until it was stable. Airway sensitivity was expressed as the ventilation (l-min-1) which provoked a 10, 15, 20 or 30% fall in FEV1, (PVE10, PVE15, PVE20 and PVE30, respectively). There was no significant difference in the PVE10,15,20,30 between the vehicle and amiloride treatment day; however, in the 8 subjects who inhaled frusemide, frusemide caused a significant increase in the PVE20 when compared to amiloride. In conclusion, inhaled amiloride failed to protect against ISH, whereas frusemide was effective at reducing airway responsiveness. Further studies are needed to explain the mechanism of action of frusemide.
Effect of frusemide on cough responses to chloride-deficient solution in normal and mild asthmatic subjects
Authors: Stone RA , Barnes PJ , Chung KF
Published: November 2022

We studied the tussive effects of a chloride-deficient solution (1.26% sodium bicarbonate). Nine normal volunteers and 10 mild asthmatic subjects were studied. In two double-blind, placebo-controlled, cross-over studies, we assessed the profile of any inhibitory effects that inhaled frusemide had over these responses. Baseline cough challenge was followed by inhalation of either frusemide (40 mg), or 0.15 M NaCl control. Cough was then induced at 0.5, 2, 4 and 6 h after treatment. Forced expiratory volume in one second (FEV1) was measured before and after each challenge. Changes from the baseline cough response due to drug or control were compared nonparametrically at each time point. There was no difference in the sensitivity of normal and asthmatic subjects to the cough challenge (median cough response 15 and 14.5 on control day, 12 and 15 on frusemide day). Frusemide caused sustained inhibition of the cough response in normal subjects (p < 0.05 at 2 h, p < 0.01 at 4 h), but had only a small, nonsignificant effect in asthmatic subjects at 30 min. Falls in FEV1 of asthmatic subjects due to the chloride-deficient solution were not significant, and did not correlate with number of coughs. We conclude that mild asthmatic subjects are less sensitive than normal subjects to the influence of frusemide against low chloride challenge. This observation is not explained by bronchoconstrictor effects of the cough challenge in asthmatic subjects.
A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. International Study Group
Authors: Barnes NC , Marone G , Di Maria GU , Visser S , Utama I , Payne SL
Published: November 2022

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom
Authors: Johnston ID , Gomm SA , Kalra S , Woodcock AA , Evans CC , Hind CR
Published: November 2022

The case notes of 200 patients with cryptogenic fibrosing alveolitis, from three regions in the United Kingdom, were reviewed, in order to determine how physicians manage this uncommon condition. In the majority of cases (119), the diagnosis was based solely on clinical grounds, with no attempt at histological confirmation of the diagnosis. Transbronchial biopsy was attempted in 66 patients, but was unhelpful in confirming a diagnosis of pulmonary fibrosis in 30% of these patients. Thirty five patients underwent bronchoalveolar lavage, and 15 had an open lung biopsy. Of the 132 patients treated, 110 received prednisolone alone, and the rest a combination of other immunosuppressive agents. The doses and duration of therapy varied considerably. These results suggest that, in the late 1980s, there were wide variations of practice in the management of cryptogenic fibrosing alveolitis in the United Kingdom. This is likely to reflect a paucity of information on the optimum management of this uncommon condition.
IgG subclasses in the lungs of patients with interstitial pneumonitis following bone marrow transplantation
Authors: Milburn HJ , Prentice HG , Grundy JE
Published: November 2022

Subclasses of immunoglobulin G (IgG) were measured in bronchoalveolar lavage (BAL) fluid and serum from five normal volunteers and 25 bone marrow transplant (BMT) recipients, who developed 32 episodes of pneumonitis. Evidence for local production of the four subclasses was sought, to assess whether any observed deficiency was associated with any particular group of pulmonary infections. In the normal volunteers, IgG1 and IgG4 could be detected in BAL fluid from all subjects, with evidence for local production of IgG1 in one, and IgG4 in all five. IgG2 could be detected in BAL fluid from one subject, but IgG3 was undetectable in all normal BAL fluid. The BMT recipients differed from the normal volunteers mainly in the presence of IgG2 and IgG3 in BAL fluid. Furthermore, IgG4 could not be detected in BAL from seven. Furthermore, IgG4 could not be detected in BAL from seven episodes of pneumonitis (six patients). Bacteria, protozoa or fungi alone were isolated from five of these seven lavages, whereas pneumonitis associated with these organisms alone only occurred in 9 of the remaining 25 episodes of pneumonitis (19 patients) where there was also evidence for local production of IgG4. Moreover, 4 out of 7 patients with no detectable IgG4 in lavage developed secondary infections, whilst only 5 out of 19 patients producing IgG4 locally developed secondary infections (p = 0.05). Although there was individual variation within each group, levels of local production of both IgG1 and IgG4 tended, however, to be higher in patients who died from pneumonitis than in those who recovered, suggesting that this may be a poor prognostic marker.(ABSTRACT TRUNCATED AT 250 WORDS)
Suppressive mechanisms of alveolar macrophages in interstitial lung diseases: role of soluble factors and cell-to-cell contact
Authors: Fireman E , Ben-Efraim S , Spinrad S , Topilsky M , Greif J
Published: November 2022

Alveolar macrophages (AMs) from patients with interstitial lung diseases, such as sarcoidosis and idiopathic pulmonary fibrosis, suppress the phytohaemagglutinin (PHA) stimulation of autologous peripheral lymphocytes. The aim of this study was to determine whether the suppressive effect of alveolar macrophages of patients with interstitial lung disease is due, not only to the secretion of soluble factors prostaglandin E2 (PGE2), interleukin-1 (IL-1) but is also correlated to a direct effect of AMs on the expression of IL-2 receptors (IL-2R: CD25) and on the induction of IL-2 activity. We studied 26 subjects, 8 with sarcoidosis, 7 with idiopathic pulmonary fibrosis, and 11 controls. Alveolar macrophages of sarcoid and idiopathic pulmonary fibrosis patients suppressed proliferation of autologous peripheral lymphocytes by 68 +/- 14% and 53 +/- 4.5%, respectively, compared to enhancement of 19 +/- 11% in three controls and suppression of 25 +/- 11% in the other six controls; the difference between subjects with interstitial lung disease and controls was significant. As already reported, the alveolar macrophages of sarcoid patients secreted large amounts of IL-1 (184 +/- 59 U.ml-1) whereas the alveolar macrophages from idiopathic pulmonary fibrosis patients secreted large amounts of PGE2 (3.6 +/- 2 ng.ml-1 x 10(-5) cells) compared with 23 +/- 19 U.ml-1 IL-1 and 0.34 +/- 0.15 ng.ml-1 x 10(-5) cells respectively, of controls. Suppression by supernatants recovered from lipopolysaccharide (LPS) stimulated alveolar macrophages can only partially explain the high suppressive effect of alveolar macrophages of interstitial lung diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
Accuracy and sensitivity of the interrupter technique for measuring the response to bronchial challenge in normal subjects
Authors: Phagoo SB , Watson RA , Pride NB , Silverman M
Published: November 2022

The interrupter technique is a non-invasive method for measuring airway calibre. Since the calculation of interrupter resistance (Rint) is critically dependent upon the analysis of the mouth pressure/time (Pmo(t)) curve obtained after flow interruption, we wanted to assess the relative merits of four different analyses of Pmo(t) curves, obtained under basal conditions and following methacholine-induced airway narrowing, in 10 healthy adults. Four methods of analysing the Pmo(t) curves were used to calculate Rint values: RintC-a smooth curve fit with back-extrapolation; RintL-two-point linear fit with back-extrapolation; RintEO-calculated from the pressure change after the post-interruption oscillations had decayed (end-oscillation); and RintEI-calculated from the pressure change at the end of the period of interruption. The airway response measured with the four Rint methods was compared with plethysmographic airway resistance (Raw). The sensitivity of the methods was determined by calculating a sensitivity index (SI), the change in resistance after challenge expressed in multiples of baseline standard deviation. Values of RintC were similar to Raw values under all conditions. Resistance values from the remaining Rint methods significantly exceeded Raw (mean basal difference: 0.13-0.34 kPa.l-1 x s; mean difference after challenge: 0.12-0.42 kPa.l-1 x s. Raw was the most sensitive method for detecting bronchoconstriction (doubling of Raw was equivalent to SI of 10.5). Of the Rint methods, RintEI gave the highest sensitivity index (SI = 3.1), with a 42% mean change; RintC produced the greatest proportionate change after challenge (55%), but with a lower SI (2.2).(ABSTRACT TRUNCATED AT 250 WORDS)
The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics
Authors: Dahlen B , Kumlin M , Margolskee DJ , Larsson C , Blomqvist H , Williams VC , Zetterstrom O , Dahlen SE
Published: November 2022

Drugs which block the action or formation of the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) inhibit asthmatic responses evoked by allergen, exercise and cold dry air. The purpose of this study was to determine whether the specific leukotriene-receptor antagonist MK-0679 could block the airway obstruction induced by aspirin (acetylsalicylic acid (ASA)) in aspirin-intolerant asthmatics. Eight asthmatics (mean age 45 yrs), with an average history of asthma and ASA-sensitivity of about 10 yrs duration, were subjected to bronchial provocation with lysine-ASA. Baseline ASA-sensitivity was first determined in an open prestudy session by inhalation of cumulative doses of lysine-ASA to establish the dose of ASA decreasing forced expiratory volume in one second (FEV1) by 20% (PD20). Rechallenge with lysine-ASA was performed on two different occasions, 1 h after oral administration of placebo, or 750 mg of MK-0679, under double-blind conditions, in a randomized, cross-over design. Leukotriene formation was estimated by the measurement of urinary LTE4. The lysine-ASA challenge was highly reproducible (geometric mean for group PD20 being identical for the open prestudy and the placebo session), and was associated with a post-challenge increase in urinary LTE4. In contrast, after MK-0679, there was a rightward shift in the dose response relationship for all eight subjects (median shift being 4.4 fold), with three of the subjects failing to produce a 20% decrease in FEV1 despite inhalation of the highest dose of lysine-ASA feasible to deliver.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelet-derived growth factor AA and AB dimers are present in normal human epithelial lining fluid
Authors: Allam M , Martinet N , Gallati H , Vaillant P , Hosang M , Martinet Y
Published: November 2022

Normal lung architecture is related to the presence of mesenchymal cells (fibroblasts and smooth muscle cells), and to the production by these cells of extracellular matrix. The turnover of mesenchymal cells is under a fine regulation due, at least in part, to the local presence of different mediators acting on their cell cycle. Since normal human alveolar macrophages obtained by bronchoalveolar lavage (BAL) spontaneously release platelet-derived growth factor (PDGF), a cytokine with chemotactic and growth activity on mesenchymal cells, we evaluated normal human epithelial lining fluid (ELF) for the presence of PDGF. Active only as a dimer, PDGF is a glycoprotein composed of two chains (A and B) and, thus, can be present in three forms: AA, AB, and BB dimers. Interestingly, normal ELF contains PDGF AA dimers, and to a lesser extent AB dimers, while no significant level of BB dimers is detected. Furthermore, ELF PDGF is biologically active and responsible for a significant part of the chemotactic activity and the "competence" growth activity for mesenchymal cells present in normal ELF. These findings suggest that ELF PDGF has a role in normal lung structure maintenance and tissue repair.
Inspiratory muscle performance relative to the anaerobic threshold in patients with COPD
Authors: Wanke T , Formanek D , Lahrmann H , Merkle M , Rauscher H , Zwick H
Published: November 2022

Rehabilitation programmes in chronic obstructive pulmonary disease (COPD) require exercise training above the anaerobic threshold. However, not all COPD patients develop metabolic acidosis during exercise. The hypothesis of this study was that non-exercise variables, characterizing the mechanical load on the inspiratory muscles during breathing at rest, can be used to reliably predict which patients with COPD are not able to develop metabolic acidosis during exercise. Thirty participants with COPD performed a symptom-limited cycle ergometer test. The oesophageal pressure/time index (PTIoes: the product of pressure magnitude and duration), the mean rate of pressure development during inspiration (Poes/TI), and the mean airway resistance (Raw)/maximal oesophageal pressure (Poesmax) ratio served as indices for the mechanical load on the inspiratory muscles. The oxygen uptake (VO2) at which plasma standard bicarbonate was seen to decrease from its baseline value was taken as the anaerboic threshold (AT). Mean Raw was significantly higher in those patients in whom the AT could not be detected. No other lung function parameters measured at rest allowed the accurate selection of those patients who did or did not develop exercise metabolic acidosis. On the other hand, Raw/Poesmax, PTIoes and Poes/TI were significantly different in the two patient groups. Additionally, whereas in the patient group with identifiable AT exercise hyperpnoea produced a non-linear increase of Poes/TI with respect to PTIoes above the AT, in the patient group without identifiable AT there was a linear relationship between Poes/TI and PTIoes throughout exercise. We conclude that the determination of inspiratory muscle load indices at rest may be useful in pulmonary rehabilitation programmes, for identifying those patients with COPD who do not develop exercise induced metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory dysfunction in congestive heart failure: correction after heart transplantation
Authors: Niset G , Ninane V , Antoine M , Yernault JC
Published: November 2022

Severe chronic congestive heart failure (CCHF) is known to induce a restrictive ventilatory defect, with a small decrease in lung transfer factor for carbon monoxide (TLCO). The aim of the present work was to assess the reversibility of this dysfunction. We studied a group of 47 patients with CCHF, before and one year after heart transplantation. The measurements included static and dynamic lung volumes, TLCO and cardiac function. On initial evaluation, vital capacity (VC), total lung capacity (TLC) and TLCO were reduced to 76, 79 and 64% of the predicted value (% pred), respectively. Forced expiratory volume in one second (FEV1) was decreased to 69% pred, with a FEV1/VC ratio below 0.70 in 13 out of 47 patients. One year after transplantation, cardiac function had markedly improved, as shown by a normalized left ventricular ejection fraction (from 18% preoperatively to 59% postoperatively), and mean pulmonary wedge pressure (from 26 to 12 mmHg). At this time, VC (94% pred) and TLC (98% pred) were within the normal range, whereas TLCO remained low (67% pred). The FEV1/VC ratio did not change, even in the subgroup with an initial low value. Smoking habits did contribute to the low TLCO and FEV1/VC ratio. In conclusion, respiratory dysfunction induced by CCHF is reversible, with the exception of the reduction in TLCO, which probably reflects permanent changes in the lung vasculature. CCHF does not induce an obstructive ventilatory pattern.
Airway inflammation in symptomatic and asymptomatic children with methacholine hyperresponsiveness
Authors: Pin I , Radford S , Kolendowicz R , Jennings B , Denburg JA , Hargreave FE , Dolovich J
Published: November 2022

A definition of asthma includes symptoms due to reversible airflow limitation and airway hyperresponsiveness. Characteristically, there is also airway inflammation. In children with methacholine airway hyperresponsiveness but no asthma symptoms, we examined whether there were features of asthmatic airway inflammation. Forty one children, aged 11-16 yrs, were studied. Thirteen asymptomatic children with methacholine airway hyperresponsiveness (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) geometric mean of 3.35 (range 1.08-7.81) mg.ml-1) were compared with 13 currently symptomatic asthmatics with a similar PC20 of 1.91 (0.42-6.5) mg.ml-1 and 13 normal children with a normal PC20 of 52.4 (17.6 to > 64) mg.ml-1. Breathlessness experienced during a methacholine test was recognized to have occurred previously in 7 out of 13 asymptomatic children and all symptomatic children. Asymptomatic children had significantly more airway responses to hyperventilation with cold dry air (4 out of 13) than normal children (0 out of 13) but less than symptomatic children (11 out of 15). Sputum induced with hypertonic saline contained lower eosinophil counts in the asymptomatic children (median (interquartile range) 0.20 (0.59)%) than in the symptomatic children (1.70 (9.45)%), and not different from the normal children (0.15 (0.61)%). Budesonide, 400 micrograms b.i.d. improved respiratory symptoms, forced expiratory volume in one second (FEV1) and methacholine PC20 in symptomatic children, but this effect did not reach statistical significance in asymptomatic children. We conclude that symptomatic children are more likely to have evidence of asthmatic inflammation than asymptomatic children and this probably explains the symptom difference.(ABSTRACT TRUNCATED AT 250 WORDS)
Human bronchial epithelial cell dysfunction following in vitro exposure to nitrogen dioxide
Authors: Devalia JL , Sapsford RJ , Cundell DR , Rusznak C , Campbell AM , Davies RJ
Published: November 2022

Nitrogen dioxide (NO2), is a major air pollutant, that causes bronchoconstriction and bronchial hyperreactivity, and may also lead to damage and inflammation of the airway epithelium. We have cultured human bronchial epithelial cells and investigated the effect of exposure to NO2, for 20 min on epithelial cell membrane integrity and function in vitro. Epithelial cell membrane damage and permeability were assessed by release of 51Cr from prelabelled cells, and movement of 14C-labelled bovine serum albumin (BSA) across the bronchial epithelial cell monolayers. Ciliary beat frequency (CBF) of the cells was monitored by the analogue contrast enhancement technique, and arachidonic acid (AA) metabolism was investigated by analysis of radiolabelled AA metabolites generated from cultures prelabelled by incubation with [3H]-arachidonic acid. Exposure to 400 and 800 parts per billion (ppb) NO2 significantly increased the release of 51Cr from 0.9 +/- 0.4%, in control cultures exposed to 5% CO2 in air, to 9.7 +/- 3.2% and 13.9 +/- 3.5%, respectively. Similarly, NO2 also significantly increased the movement of 14C-BSA across the epithelial monolayers from 1.3 +/- 0.2%, in control cultures, to 2.7 +/- 0.2%, 3.8 +/- 0.4% and 5.1 +/- 0.5%, respectively, in cultures exposed to 100, 400 and 800 ppb NO2. Although NO2 attenuated the CBF of the cells at all concentrations investigated, this was significant only at the concentration of 2,000 ppb NO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of pulmonary hypertension on gas exchange
Authors: Agusti AG , Rodriguez-Roisin R
Published: November 2022

This paper reviews the effects of pulmonary artery hypertension on gas exchange by exploring three different issues, namely: 1) how does gas exchange behave in diseases characterized by increased vascular tone (primary pulmonary hypertension (PPH), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF)) or decreased vascular tone ("hepatopulmonary syndrome"); 2) how does exercise, as a non-pharmacological tool of increasing pulmonary blood flow, modify gas exchange in these diseases; and 3) how do several drugs that lower (vasodilators) or increase (almitrine) the active component of pulmonary hypertension interact with gas exchange. Available data show that: 1) in PPH a high pulmonary vascular tone enhances gas exchange and when it is lowered, either by oxygen or vasodilators, ventilation perfusion (VA/Q) distributions deteriorate; 2) in COPD a lowered (vasodilators) or augmented (almitrine) active vascular tone is almost invariably paralleled by a deterioration or enhancement of ventilation-perfusion matching, respectively; 3) in IPF an adequate active response of the pulmonary vasculature is essential to maintain gas exchange, both at rest and during exercise; and 4) in patients with liver cirrhosis a low pulmonary vascular tone induces an abnormal VA/Q distribution. In summary, these data show that any situation and/or therapeutic intervention that lowers the active vascular tone deteriorates VA/Q relationships and vice versa. The final effect of pulmonary vascular tone on arterial oxygen tension (PaO2) is less predictable. The reason for this uncertainty is that the actual PaO2 value depends on the interplay of the intra- and extrapulmonary factors that control gas exchange in humans, and not only on the degree of VA/Q mismatching.
Cost-effectiveness of a structured treatment and teaching programme on asthma
Authors: Trautner C , Richter B , Berger M
Published: November 2022

The purpose of this study was to perform a cost-effectiveness analysis of the structured treatment and teaching programme for patients with asthma (ATTP) at Dusseldorf University. We investigated whether the monetary benefits outweighed the costs of the intervention. Adult patients with moderate to severe asthma participated in a 5 day in-patient programme. Follow-up was 3 yrs. The incremental costs and benefits of the intervention, compared with standard treatment, were calculated. Costs were incurred by the hospitalization and by lost productivity. Compared to the year before the programme, (average reduction) days spent in hospital (5.2 days per patient per year), days of absence from work (18.4 days per patient per year), acute severe asthma attacks (3.8 attacks per patient per year), and physician consultations (2.3 visits per patient per month), decreased in the 3 yrs after the intervention. The programme produced net benefits of DM 12,850 (in 1991 German marks) per patient within 3 yrs. Within the health care sector, the net benefits were DM 5,900. Within 3 yrs, the paying bodies saved DM 2.70, and society as a whole saved DM 5 on each DM spent for the programme. We conclude that the intervention produced net monetary benefits. This result was stable over a wide range of variation of the outcome measures. Therefore, programme deserves implementation, not only for its demonstrated medical benefits but also for its economic savings.
Bronchodilating effect of ipratropium bromide in heart failure
Authors: Rolla G , Bucca C , Brussino L , Gallo W , Malara D
Published: November 2022

The aim of this study was to test the hypothesis that lung oedema causes an obstructive airway impairment, due to an increase in cholinergic bronchial tone in patients with chronic heart failure (CHF). Ten patients with CHF were tested by inhalation of ipratropium bromide and placebo, given in sequential randomized order, in double-blind fashion, after assessment of baseline lung function, both during acute cardiac decompensation and after 8-10 days of adequate treatment. The decrease in lung oedema was associated with a significant increase in vital capacity (VC) (from 70 +/- 4.4 to 83 +/- 5.4% pred), forced expiratory volume in one second (FEV1) (from 59 +/- 3.6 to 72 +/- 4.6% pred), FEV1/VC (from 61 +/- 2.8 to 64 +/- 2.3%) and residual volume (RV) (from 94 +/- 7.9 to 99 +/- 6.8% pred). Ipratropium bromide produced a far better bronchodilatation during acute decompensation when FEV1 increased from 59 +/- 3.6 to 70 +/- 3.7% pred, than after intensive treatment for heart failure, when FEV1 increased from 72 +/- 4.6 to 76 +/- 4.8% pred. The maximum absolute increase in FEV1 induced by ipratropium bromide was 286 +/- 32 ml at admission and only 111 +/- 15 ml after treatment. In conclusion, in chronic heart failure, airway obstruction is partially reversible after inhalation of an anti-muscarinic drug, when lung oedema is present, supporting the hypothesis that lung oedema increases cholinergic bronchial tone.
Medical treatment of pulmonary hypertension in acute lung disease
Authors: Naeije R
Published: November 2022

A moderate pulmonary hypertension is a hallmark of experimental, as well as clinical, acute lung injury. Pulmonary hypertension in acute lung injury, appears to be caused primarily by a partially reversible increase in extra-alveolar vascular closing pressure, the latter being modulated by vasodilating products of the cyclooxygenase pathway of arachidonic acid metabolism, as well as by an endogenous release of nitric oxide. Gas exchange in acute lung injury is improved by increased pulmonary vascular tone. However it is also improved by inhaled nitric oxide, which increases perfusion to the better aerated lung areas. Whether pharmacological interventions aimed at the prevention of right ventricular failure in acute lung injury improve right ventriculo-vascular coupling sufficiently to exert a favourable influence on outcome, remains to be shown.
Selective intrabronchial instillation of surfactant in a patient with pneumonia: a preliminary report
Authors: Mikawa K , Maekawa N , Nishina K , Takao Y , Yaku H , Obara H
Published: November 2022

The efficacy of treatment with exogenous surfactant has been reported in children with respiratory failure due to severe pneumonia. Its effect in adults with similar features has not been established. We therefore administered 240 mg of surfactant to a 71 year old man, who had developed right lower lobe pneumonia and hypoxaemia following abdominal aortic surgery. After this treatment, the patient's oxygenation, evaluated by arterial oxygen tension/fraction of inspired oxygen (PaO2/FIO2) ratio during artificial ventilation, gradually improved, and ventilator settings could be reduced whilst maintaining PaO2 at the appropriate level. Although the precise mechanism by which surfactant improves respiratory failure due to pneumonia is unclear, administration of the drug may have overcome a quantitative deficiency of endogenous surfactant attributable to the antagonistic effect of pulmonary exudates and reduced production following damage to type II pneumocytes. The present case provides an indirect suggestion of a possible causal relationship between the improvement of oxygenation and administration of surfactant in adult respiratory failure caused by pneumonia.
Skin lesions and an intrathoracic mass
Authors: Vasmel WL , van Mourik JC , Jiwa MN , Postmus PE
Published: November 2022

We describe a case of thoracic actinomycosis in a previously healthy man. The clinical features were a paramediastinal mass with skin lesions due to haematogenic dissemination. After parasternal mediastomy, the diagnosis was made. After treatment with penicillin, there was complete recovery.
Integrated analyses reveal the response of peanut to phosphorus deficiency on phenotype, transcriptome and metabolome
Authors: Wu Qi , Yang Liyu , Liang Haiyan , Yin Liang , Chen Dianxu , Shen Pu
Published: November 2022

Background

Phosphorus (P) is one of the most essential macronutrients for crops. The growth and yield of peanut (Arachis hypogaeaL.) are always limited by P deficiency. However, the transcriptional and metabolic regulatory mechanisms were less studied. In this study, valuable phenotype, transcriptome and metabolome data were analyzed to illustrate the regulatory mechanisms of peanut under P deficiency stress.

Result

In present study, two treatments of P level in deficiency with no P application (–P) and in sufficiency with 0.6 mM P application (+ P) were used to investigate the response of peanut on morphology, physiology, transcriptome, microRNAs (miRNAs), and metabolome characterizations. The growth and development of plants were significantly inhibited under –P treatment. A total of 6088 differentially expressed genes (DEGs) were identified including several transcription factor family genes, phosphate transporter genes, hormone metabolism related genes and antioxidant enzyme related genes that highly related to P deficiency stress. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that 117 genes were annotated in the phenylpropanoid biosynthesis pathway under P deficiency stress. A total of 6 miRNAs have been identified significantly differential expression between + P and –P group by high-throughput sequencing of miRNAs, including two up-regulated miRNAs (ahy-miR160-5p and ahy-miR3518) and four down-regulated miRNAs (ahy-miR408-5p, ahy-miR408-3p, ahy-miR398, and ahy-miR3515). Further, the predicted 22 target genes for 6 miRNAs andcis-elements in 2000 bp promoter region of miRNA genes were analyzed. A total of 439 differentially accumulated metabolites (DAMs) showed obviously differences in two experimental conditions.

Conclusions

According to the result of transcripome and metabolome analyses, we can draw a conclusion that by increasing the content of lignin, amino acids, and levan combining with decreasing the content of LPC, cell reduced permeability, maintained stability, raised the antioxidant capacity, and increased the P uptake in struggling for survival under P deficiency stress.