bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of maximal airway narrowing to methacholine between children and adults
Authors: de Pee S , Timmers MC , Hermans J , Duiverman EJ , Sterk PJ
Published: November 2022

Bronchial hyperresponsiveness in adults is characterized by an increased sensitivity as well as an elevated maximal response to inhaled bronchoconstrictors. In children, however, it is unknown whether the maximal response increases with increasing sensitivity. We investigated the maximal degree of airway narrowing to methacholine in nonasthmatic and asthmatic children (7-12 yrs), and compared it to that in adults. Nineteen children (9 normals, 10 asthmatics) and 19 adults (8 normals, 11 asthmatics) were selected in order to cover a wide distribution of bronchial responsiveness. All subjects underwent 2 methacholine challenge tests on separate days, by inhaling doubling doses using a standardized dosimeter technique (up to a noncumulative dose of 59 mumol). The response was measured by forced expiratory volume in one second (FEV1) and expressed as a percentage fall from baseline value. The complete dose-response curves were characterized by their position (PD20, the provocative dose causing a 20% fall in FEV1) and maximal response (MFEV1, the mean response on the plateau, defined as greater than or equal to 2 points within a 5% response range). Plateaus were observed in 13 children and 9 adults, the coefficient of repeatability of MFEV1 being 10.8 and 10.4% fall, respectively. There was an inverse relationship between log PD20 and MFEV1, which did not differ between children and adults (p greater than 0.15). In most of the asthmatic children and adults the plateau could not be measured (exceeding 50% fall in FEV1) if PD20 was less than 1 mumol. We conclude that, for a given bronchial sensitivity, the maximal response to inhaled methacholine is similar between children and adults.(ABSTRACT TRUNCATED AT 250 WORDS)
Mortality and morbidity from respiratory diseases in childhood in The Netherlands, 1980-1987
Authors: Wever-Hess J , Wever AM , Yntema JL
Published: November 2022

National mortality and hospitalization data from the Netherlands were analysed for asthma (International Classification of Diseases) (ICD 493), acute bronchi(oli)tis (ICD 466), pneumonia and influenza (ICD 480-487), and other chronic obstructive pulmonary diseases (ICD 490 + 491 + 492 + 496) in children aged 0-14 yrs for 1980-1987. No trends were seen in the mortality in age groups 0-4 yrs and 5-14 yrs, which actually concerned small numbers. In general a tendency towards increasing hospital admission rates for respiratory diseases was observed in both sexes in age groups 0-4 yrs and 5-9 yrs but not in age group 10-14 yrs, and significant increases were found for asthma in males and females aged 0-4 yrs and in males aged 5-9 yrs, and for acute bronchitis in females aged 5-9 yrs. Hospital admission rates in the Netherlands for asthma appeared to be low compared to other countries. The average length of stay, however, for both asthma and the other respiratory diseases was substantial though declining. Clinical information is required on possible causal factors of the apparent need for hospitalization for reactive airway disorders in young children, and on the management of asthma in particular.
A single-compartment model cannot describe passive expiration in intubated, paralysed humans
Authors: Chelucci GL , Brunet F , Dall'Ava-Santucci J , Dhainaut JF , Paccaly D , Armaganidis A , Milic-Emili J , Lockhart A
Published: November 2022

The time-course of thoracic volume changes (respiratory inductive plethysmograph) during relaxed expiration was studied in 11 intubated, paralysed, mechanically ventilated subjects. The semilog volume-time curves show that expiration is governed by two apparently separate mechanisms: one causes emptying of most of the expired volume (approximately 80%) with a time constant of 0.50 +/- 0.22 s for a baseline tidal volume of 0.44 +/- 0.12 l (mean +/- SD) and 0.37 +/- 0.14 s when the tidal volume is reduced (VTP); the other contributes a relatively small amount to the expired volume over a significantly longer time, the time constant amounting to 3.27 +/- 1.54 s for baseline VT and 2.95 +/- 1.65 s for VTp. The first mechanism probably reflects the standard elastic and flow resistive properties of the respiratory system, while the second, slower compartment, is probably an expression of the viscoelastic properties of the pulmonary and chest wall tissues.
Aerosolized endothelin-1, but not its C-terminal hexapeptide, causes airway narrowing in the rat
Authors: Di Maria GU , Bellofiore S , Malatino LS , Maggi CA , Torrisi A , Mistretta A
Published: November 2022

We investigated the effects of aerosolized endothelin-1 (ET-1) and of its C-terminal hexapeptide, ET-(16-21), on the pulmonary mechanics of anaesthetized spontaneously-breathing rats. ET-1 inhalation caused a concentration-dependent increase in pulmonary resistance (RL) and decrease in dynamic lung compliance (Cdyn). In control conditions RL and Cdyn were 0.17 +/- 0.04 cmH2O.ml-1.s (mean +/- SE; n = 6) and 6.25 +/- 0.66 ml.cmH2O.1. respectively. After ET-1 4 x 10(-5) M RL and Cdyn averaged 1.45 +/- 0.28 cmH2O.ml-1.s (p less than 0.05) and 1.12 +/- 0.36 ml.cmH2O-1 (p less than 0.05), respectively. The pulmonary responses to ET-1 lasted up to 60 min. By contrast, ET-(16-21) inhaled up to a concentration of 10(-3) M did not affect pulmonary mechanics. These results indicate that the bronchoconstrictor activity of aerosolized endothelin-1 in the rat is not dependent on its C-terminal sequence, and suggests a role for endothelin-1 in the regulation of airway calibre.
Lack of effect of dextromethorphan on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease (COPD)
Authors: Giron AE , Stansbury DW , Fischer CE , Light RW
Published: November 2022

We have previously shown that the exercise performance of patients with severe chronic obstructive pulmonary disease (COPD) can be increased with the administration of oral morphine (0.8 mg.kg-1). The purpose of this study was to determine whether the administration of dextromethorphan (DXT), an antitussive structurally similar to codeine, would result in increased exercise performance and decreased dyspnoea in patients with COPD, without the side-effects of opiates. Six eucapnic patients (mean age = 66 +/- 3.8 yrs) with COPD (mean forced expiratory volume in one second (FEV1) = 1.01 +/- 0.07 l) underwent two incremental cycle ergometer tests to exhaustion (Emax) and assessment of their hypercapnic and hypoxic ventilatory responses and mouth occlusion pressure responses following first the oral administration of placebo (P) and then dextromethorphan (60 mg) in a single-blind fashion. There was no statistically significant difference in the maximal exercise performance, perceived dyspnoea (modified Borg scale), breathing pattern or expired gases after the two different treatments. In addition, the ventilatory response to CO2 production during exercise (delta VE/VCO2) and the ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia did not differ significantly after DXT as compared with after P. Indeed the exercise performance was poorer and the ventilatory responses were brisker after DXT. We conclude from this study that the administration of this opiate analogue does not improve the exercise capacity or decrease the ventilatory response of patients with COPD.
Effects of PEEP on respiratory mechanics in patients with COPD on mechanical ventilation
Authors: van den Berg B , Stam H , Bogaard JM
Published: November 2022

We studied the effects of positive end-expiratory pressure (PEEP) applied by the ventilator on respiratory mechanics in ventilated patients with chronic obstructive pulmonary disease (COPD). Airway pressures, relaxed expiratory flow-volume curves and end-expiratory volumes (EEV) were measured. In all patients investigated without PEEP applied by the ventilator, an intrinsic PEEP level (PEEPi) and a concavity in the flow-volume curve was present. Ventilator-PEEP caused a significant decrease in PEEPi in all patients (p less than 0.01). In patients in whom ventilator-PEEP exceeded PEEPi, significant increases occurred in airway pressures and EEV (p less than 0.05) and moreover the shape of the flow-volume curve was changing. In patients in whom the level of ventilator-PEEP was below the PEEPi level, no significant changes in airway pressures, EEV or flow-volume curves were found. We conclude: 1) PEEP applied by the ventilator can reduce PEEPi in ventilated patients with COPD without significant changes in airway pressures, EEV or flow-volume curves. 2) Expiratory flow-volume curves can be used to estimate the effects of ventilator-PEEP on EEV.
Airway cooling: stimulus specific modulation of airway responsiveness in the canine lung periphery
Authors: Freed AN , Stream CE
Published: November 2022

We used a wedged bronchoscope technique in conjunction with an in situ isolated perfused left lower lobe preparation in anesthetized dogs to examine cold-associated airway modulation of peripheral lung responses to dry airflow, hypocapnia, and aerosols of histamine and hypertonic NaCl. In this preparation, airway wall temperature was rapidly lowered by decreasing the temperature of blood perfusing the wedged sublobar segment. Cooling significantly attenuated responses to dry air, hypertonic NaCl aerosol, and hypocapnic challenge. In contrast, cooling did not affect peripheral lung responses to aerosolized histamine. Thus, cooling per se does not inhibit the responsiveness of smooth muscle. We conclude that, depending on the stimulus, cooling can modulate airway reactivity. We speculate that cooling attenuates hypocapnia, hypertonic aerosol, and dry air-induced bronchospasm via a cold induced reduction in neuronal activity or mediator production and release.
Accuracy, precision and linearity of the portable flow-volume meter Microspiro HI-298
Authors: Dompeling E , van Schayck CP , Folgering H , van den Hoogen HJ , van Weel C
Published: November 2022

The accuracy, precision and linearity of a new portable flow-volume meter, the Microspiro HI-298 (Chest Corporation, Tokyo, Japan), was investigated using a Fleisch no. 4 pneumotachograph as a standard. After connection and calibration of the pneumotachograph and the Microspiro, a healthy subject performed 44 forced vital capacity (FVC) manoeuvres at different levels of lung inflation. The FVC of these expirations ranged from 2.5-5.1 l. Linear regression of Microspiro values (dependent variable) on Fleisch pneumotachograph values (independent variable) showed that a good linear relationship existed: Pearson correlation coefficients ranged from 0.938-0.985. Linearity of the Microspiro was good except for the peak expiratory flow rate (PEFR) and the maximal expiratory flow at 25% of the expired volume (MEF75). The random error (measure of precision) of all flow-volume (F-V) indices was lower than 5%. The systematic error (measure of accuracy) was low for the forced expiratory volume in one second (FEV1) and the FVC (1% and 4.6%, respectively) but much higher for the instantaneous expiratory flows (PEFR 11.0%; MEF75 7.0%; MEF50 8.5%; MEF25 11.4%). Only the total error in FEV1 complied with the tolerance of 4% of the European Community for Coal and Steel (ECCS). When the measured values were adjusted according to the regression equations of this study, all F-V indices were accurate and precise within 5%. It was concluded that the portable Microspiro HI-298 is a useful instrument for bedside, work-site spirometry and for use in general practice.(ABSTRACT TRUNCATED AT 250 WORDS)
Ciliary beat frequency and structure of recipient and donor epithelia following lung transplantation
Authors: Read RC , Shankar S , Rutman A , Feldman C , Yacoub M , Cole PJ , Wilson R
Published: November 2022

To investigate possible changes following lung transplantation, the structure and in vitro ciliary beat frequency (CBF) of airway epithelium from the cytology brushings of 9 heart-lung (HLT) and 5 single-lung (SLT) transplant recipients were examined. The CBF of brushings taken proximal and distal to the anastomosis was measured 2-10 months following transplant. There was no difference between the measured mean CBF at the two sites or between the two groups; HLT CBF: distal 11.0 +/- 0.5 Hz (standard error of mean), proximal 10.5 +/- 0.4 Hz, SLT CBF: distal 11.7 +/- 0.9 Hz, proximal 12.0 +/- 0.6 Hz. Mean CBF of bronchial brushings (except distal brushings from SLT patients) was significantly lower than that from controls: 13.6 +/- 0.3 Hz (n = 7) (p less than 0.05). Transmission electron microscopy of epithelial brushings from 4 patients (3 HLT, 1 SLT) revealed epithelial abnormalities both proximal and distal to the anastomosis, particularly ciliary depletion, mitochondrial abnormalities and death of cells. No significant ciliary ultrastructural abnormalities were seen in any tissue. We conclude that epithelial abnormalities were observed both proximal and distal to the anastomosis following lung transplantation. These may contribute to impairment of mucociliary clearance.
The alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduce nasal potential difference
Authors: Wood AM , Dinh Xuan AT , Cremona G , Lockhart A , Higenbottam TW
Published: November 2022

Pretreatment by inhalation with the alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduces the bronchial response to certain airway challenges in asthma. To test whether these drugs may act by altering airway epithelial ion and water transport, their effect on nasal potential difference (PD) when applied topically in eight normal volunteers was measured. For comparison, the effect of the Na(+)-channel blocking drug amiloride and the beta 2-adrenergic agonist salbutamol was also tested. Both methoxamine and frusemide significantly reduced PD: at the highest concentration given (10(-3) mol.l-1), there was a mean drop in PD from baseline of 39.5% following methoxamine treatment (p less than 0.05) and a mean drop of 30.2% following frusemide (p less than 0.05). Neither drug was as effective as amiloride, which caused a mean drop in PD of 27.5% from baseline at 10(-6) mol.l-1 and a drop of 71.6% at 10(-3) mol.l-1 (p less than 0.01 for each concentration). Salbutamol had no significant effect on PD (p greater than 0.05). We conclude that methoxamine and frusemide may derive their protective effect on some bronchial challenge, at least in part, from their effect on airway epithelial ion flux.
Effects of tobacco smoke on respiratory epithelial clearance of DTPA and on lung histology in rats
Authors: Mordelet-Dambrine M , Leguern-Stanislas G , Chinet TC , Barritault L , Chretien J , Huchon GJ
Published: November 2022

The respiratory epithelial clearance of 99mTc-(DTPA) diethylenetriamine penta-acetate (RC-DTPA) was measured in rats before and after sham or cigarette smoke exposures. RC-DTPA was increased by cigarette smoke exposure (p less than 0.001); the amount and duration of the exposure had no significant effect. In smoker animals, the number of bronchoalveolar macrophages was decreased after one or five smoke exposures a day for one day (p less than 0.001) and the number of bronchoalveolar neutrophils was increased after five exposures a day for ten days (p less than 0.001). No abnormality was found in the lung parenchyma on light microscopy. We conclude that in rats RC-DTPA is increased by exposure to tobacco smoke, whatever the amount and duration of exposure; however, no gross parenchymal lung abnormality explains the increase in RC-DTPA.
A review of the racial differences in the lung function of normal Caucasian, Chinese and Indian subjects
Authors: Yang TS , Peat J , Keena V , Donnelly P , Unger W , Woolcock A
Published: November 2022

In the clinic, predicted normal values are widely used for routine assessments and, therefore, it is important that the noted differences in lung volumes between the races are recognized. Further epidemiological studies, using comparative methods and standard statistical techniques, are essential in order to quantify apparent differences between the races and to standardize normal values for race, especially with regard to age, with greater accuracy.
Glucocorticosteroid therapy in acute severe asthma--a critical review
Authors: Engel T , Heinig JH
Published: November 2022

Glucocorticosteroid (GCS) therapy is one of the corner-stones in the treatment of asthma. Its value in acute severe asthma is still open for debate. Many of the papers published on the topic are subject to methodological problems. In 8 of 13 placebo-controlled studies, GCS therapy proved to be superior to placebo, evaluated either as result of pulmonary function, blood gas tension, or hospital admission rate. The most important point for GCS therapy in acute severe asthma seems to be frequent dosage, typically 4 times daily. Oral and intravenous administration seem to have equal efficacy. Only 2 of 10 studies were able to prove a dose-response relationship. Both studies included very low doses of GCS. Doses of 100-200 mg of methylprednisolone for 24 h seem as effective as high doses. A protective effect against relapses within a certain time after the GCS therapy has been demonstrated only for periods not exceeding 4 weeks, and only in children. So far, no study has been able to depict the categories of patients who may or may not benefit by the addition of GCS therapy to the symptomatic treatment of acute severe asthma.
Increased lung deposition and biological effect of methacholine by use of a drying device for bronchial provocation tests
Authors: Malmberg P , Larsson K , Thunberg S
Published: November 2022

A simple device aiming to increase deposition of nebulized methacholine in the lower airway was studied. The device controlled inspiratory flow and volume and dried the aerosol. The effect of drying on deposition in the throat and lower airways was studied in six subjects given an aerosol of 99mTechnetium-diethylenetriamine pentaacetate (DTPA) in saline with the device and with a reference device giving the same inspiratory flow and volume but no drying. Drying reduced throat deposition from 46 (range 26-61) to 13 (range 6-22)% (p less than 0.05) of the inhaled and retained dose. The effect of drying on the biological effect of nebulized methacholine was studied in 21 subjects who underwent three provocation tests on different days with doubling concentrations of methacholine from 0.5 to a maximum of 64 mg.ml-1, one with the reference device and two with the drying device. The percentage change in forced expiratory volume in one second (%FEV1) per cumulative dose of methacholine changed from -1.0 (2.6) %FEV1.mumol-1 (geom. mean and SD) with the reference device to -1.6 (3.6) with the drying device p less than 0.02. In an additional study 20 subjects underwent four provocation tests on different days, two with a different version of the drying device and two with the reference device. The slope changed from -1.1 (3.1) to -1.6 (3.3), p less than 0.02. The reproducibility of duplicate measurements did not improve with the drying device. Thus, the drying device decreased throat deposition and increased the biological effect of nebulized methacholine.
Immunoglobulin G subclasses and spirometry in patients with chronic obstructive pulmonary disease
Authors: O'Keeffe S , Gzel A , Drury R , Cullina M , Greally J , Finnegan P
Published: November 2022

Immunoglobulin G (IgG) subclass levels were measured in 58 patients with chronic obstructive pulmonary disease (COPD) and in 125 healthy controls. Total IgG values were significantly lower in the 27 COPD patients on steroid therapy compared with patients not taking steroids (8.31 (0.14) vs 9.80 (0.14), p less than 0.05), geometric mean (log SD). Total IgG (9.80 (0.14) vs 12.18 (0.16), p less than 0.005), IgG1 (5.87 (0.19) vs 6.68 (0.12), p less than 0.05) and IgG2 levels (2.75 (0.21) vs 3.70 (0.20), p less than 0.005) were significantly reduced in the COPD patients not taking steroids compared with the controls. IgG3 values were significantly elevated in smokers compared with nonsmokers in both the control and COPD groups. Fifteen COPD patients (25.9%) had a low level of one or more subclasses. IgG2 subclass deficiency was the most common, being present in 9 patients. A significant correlation was found between forced expiratory volume in one second (FEV1) and IgG2 subclass levels (r = 0.415; p less than 0.005). IgG subclass deficiencies may contribute to the development and progression of respiratory disease in COPD patients.
Inherited factors in diffuse bronchiectasis in the adult: a prospective study
Authors: Verra F , Escudier E , Bignon J , Pinchon MC , Boucherat M , Bernaudin JF , de Cremoux H
Published: November 2022

To evaluate the prevalence of inherited respiratory ciliary structure and underlying mucus abnormalities in the diffuse bronchiectasis syndrome, we investigated 53 subjects comprising 38 patients with diffuse bronchiectasis confirmed by high-resolution thoracic computed tomography, ten with chronic bronchitis and no diffuse bronchiectasis and five healthy nonsmoking control subjects. The clinical history was determined by means of a standardized questionnaire. Axonemal abnormalities of respiratory cilia were evaluated on bronchial or nasal mucosa samples by transmission electron microscopy (structure) and stroboscopic observation (function). Cystic fibrosis (CF) and Young's syndrome were detected by means of the sweat test and semen analysis when male infertility was suspected. Among the 38 patients with diffuse bronchiectasis, a primary ciliary dyskinesia (PCD) was detected in five (13%) with a high proportion (range: 55-100%) of cilia showing axonemal ultrastructural abnormalities always involving the dynein arms. The prevalence of this inherited condition was higher in North African (36%) than in European patients (4%) (p less than 0.01). After exclusion of the five patients with PCD, the patients with diffuse bronchiectasis showed axonemal ultrastructural abnormalities similar to those with chronic bronchitis. The diagnosis of underlying mucus disorders was based on two types of criterion, i.e. for CF, sweat chloride levels greater than 80 mmol.l-1, or the combination of diagnostic criteria proposed by Stern et al. Respectively, five (three Young's syndrome and two CF) and seven (one Young's syndrome and six CF) cases of inherited mucus disorders were suspected. Our results showed that PCD was highly prevalent among the adult North African patients with diffuse bronchiectasis but relatively rare in the Europeans.
Correlations between findings at computed tomography (CT) and at thoracoscopy/thoracotomy/autopsy in pleural mesothelioma
Authors: Maasilta P , Vehmas T , Kivisaari L , Tammilehto L , Mattson K
Published: November 2022

Thirty five computed tomography (CT) scans of the thorax and upper abdomen of thirty three patients with malignant pleural mesothelioma were correlated with the findings at thoracotomy (28 patients), thoracoscopy (2 patients) or autopsy (5 patients). Pleural thickening with contrast medium enhancement was detected on the CT scans of all patients. This finding was a valuable diagnostic tool, especially in cases of large amounts of pleural effusion and/or only thin layers of tumour barely or not at all visible on plain film chest X-rays. Difficulties in defining the exact extent of the diseases for clinical staging and/or evaluation of treatment response arose at the following sites: diaphragmatic pleura, chest wall, pericardium, mediastinum and mediastinal lymph nodes. Extension into the lung was difficult to identify following chemo- and/or radiotherapy. Our results show that CT is essential in the clinical management of mesothelioma. We recommend that CT scans of the chest and upper abdomen, using contrast medium enhancement, should be required in routine practice and in particular in clinical trials involving pleural mesothelioma.
Inhaled nedocromil sodium as additional treatment to high dose inhaled corticosteroids in the management of bronchial asthma
Authors: Svendsen UG , Jorgensen H
Published: November 2022

Thirty five asthmatic patients were included in a randomized, double-blind, placebo-controlled, parallel group study of inhaled nedocromil sodium (4 x 4 mg daily) as an additional treatment to high dose (greater than or equal to 1,000 micrograms) inhaled corticosteroids in the management of bronchial asthma. Following a four week baseline, patients received nedocromil sodium (17) or placebo treatment (18) for eight weeks. Five patients (four in the group subsequently randomized to nedocromil sodium) used short course oral corticosteroid therapy during the baseline and four placebo treated patients used oral steroid therapy during treatment. Fifteen patients (11 nedocromil sodium) reported unusual symptoms. Two nedocromil sodium treated patients were withdrawn owing to treatment taste and vomiting. Statistically significant treatment differences in favour of nedocromil sodium were seen for daytime symptoms (p = 0.03) and morning peak expiratory flow (PEF) (p = 0.012) during weeks 5-8, and for clinician opinion (p = 0.02). Patient opinion (p = 0.053) and evening PEF (p = 0.08) failed to reach statistical significance. Eight out of fifteen and three out of seventeen patients considered nedocromil sodium and placebo, respectively, to be very or moderately effective. The results indicate that the addition of nedocromil sodium (4 mg four times daily) to moderate to severe asthmatics not fully controlled on a regimen of greater than or equal to 1,000 micrograms inhaled corticosteroids and inhaled bronchodilators can produce improvements in symptoms and pulmonary function.
Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response
Authors: Milledge JS , Beeley JM , Broome J , Luff N , Pelling M , Smith D
Published: November 2022

In a party of 17 subjects who travelled together to 4,500 m, hypoxic ventilatory response (HVR) and maximum oxygen consumption (VO2max) were measured before departure. HVR was measured under constant and varying alveolar carbon dioxide tension (PACO2) conditions. VO2max was measured by both standard expired gas collection technique on a treadmill and using the "shuttle run" technique. On arrival at altitude, symptoms of acute mountain sickness (AMS) were scored daily for three days. There were no cases of severe AMS but half of the party had mild to moderate degrees of AMS. There was no correlation between AMS scores and HVR by either method of measurement or with VO2max measured by either method of measurement or with VO2max measured by treadmill or shuttle run.
Toxic effects of oxygen on cultured alveolar epithelial cells, lung fibroblasts and alveolar macrophages
Authors: Housset B , Hurbain I , Masliah J , Laghsal A , Chaumette-Demaugre MT , Karam H , Derenne J
Published: November 2022

Exposure to hyperoxia results in endothelial necrosis followed by type II cell proliferation. This suggests that type II cells are resistant to hyperoxia. Oxygen-induced lung injury may result from an overproduction of oxygen metabolites normally scavenged by antioxidants such as superoxide dismutase (SOD), glutathione peroxidase, catalase and reduced glutathione (GSH). Therefore, resistance of type II cells to hyperoxia may be linked to high antioxidant activities. To test this hypothesis we compared in vitro the effects of a 24 h exposure period to 95% O2 on cultured type II cells, lung fibroblasts and alveolar macrophages isolated from rats. We show that type II cells, when compared with other cell types, are highly sensitive to hyperoxia as shown by increased lactate dehydrogenase (LDH) release, decreased deoxyribose nucleic acid (DNA) and protein content of Petri dishes and decreased thymidine incorporation into DNA. Synthesis of dipalmitoylphosphatidylcholine was also significantly reduced. Antioxidant enzyme activities as well as glutathione content were not higher in type II cells than in other cell types. However, hyperoxia results in a decreased SOD activity and glutathione content in type II cells which was not observed in fibroblasts. We conclude that adaptative changes in SOD and glutathione metabolism could be important defence mechanisms in cells exposed to hyperoxia.
Effect of nebulized salbutamol in preterm infants during the first year of life
Authors: Yuksel B , Greenough A
Published: November 2022

The acute effect on lung function of nebulized salbutamol and saline (placebo) has been investigated in preterm infants at follow-up. Twenty two premature infants, median gestational age 29 weeks (range 26-32 weeks) and birthweight 1,264 g (720-1,800 g), were studied at a median postnatal age of 7 months (range 6-9 months). Nine of the infants had recurrent respiratory symptoms; they coughed and/or wheezed at least 3 days per week for the previous 4 weeks. The remaining 13 infants were free from recurrent or persistent respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (Raw) were measured and specific airway conductance sGaw calculated before and 10 min after salbutamol and normal saline given via a nebulizer. Amongst the symptomatic infants administration of nebulized salbutamol was associated with a median reduction in Raw of 25% (p less than 0.01) and also a significant improvement in sGaw (p less than 0.01). In the asymptomatic infants neither Raw nor sGaw changed significantly. Nebulized saline caused no significant change in lung mechanics in either the symptomatic or asymptomatic infants. We conclude that nebulized salbutamol is an effective bronchodilator for symptomatic preterm infants less than one year of age.
Inhaled budesonide in chronic bronchitis. Effects on respiratory impedance
Authors: Wesseling GJ , Quaedvlieg M , Wouters EF
Published: November 2022

In a placebo controlled study the effects of 6 weeks' treatment with inhaled budesonide (1.6 mg daily) on the impedance of the respiratory system, spirometry and symptom scores were evaluated in 35 patients with chronic bronchitis with forced expiratory volume in one second (FEV1) greater than or equal to 70% predicted. Thirty patients completed the study. No statistically significant differences in the changes in morning peak expiratory flow rate (PEFR), symptom scores, use of terbutaline rescue medication and FEV1 were found between the placebo and the active treatment group. Budesonide treatment was found to result in a small decrease in resonant frequency and a less negative frequency dependence of resistance compared with the placebo group.
Chronic obstructive pulmonary disease and anaesthesia: formation of atelectasis and gas exchange impairment
Authors: Gunnarsson L , Tokics L , Lundquist H , Brismar B , Strandberg A , Berg B , Hedenstierna G
Published: November 2022

Gas exchange impairment and the development of atelectasis during enflurane anaesthesia were studied in 10 patients (mean age 70 yrs) with chronic obstructive pulmonary disease (COPD). Awake, no patient displayed atelectasis as assessed by computed X-ray tomography. The ventilation/perfusion distribution (VA/Q), studied by the multiple inert gas elimination technique, displayed an increased dispersion of VA/Q ratios (the logarithmic standard deviation of the perfusion distribution, mean log Q SD 0.99; upper 95% confidence limit of normal subject: 0.60), and increased perfusion of regions with low VA/Q ratios (0.005 less than VA/Q less than 0.1: 5.4% of cardiac output). Shunt was negligible (mean 0.6%). Computed chest tomography showed significantly larger cross-sectional thoracic areas than previously seen in subjects with healthy lungs (p less than 0.01). No atelectasis was seen in any patient. During anaesthesia there was a further worsening of the VA/Q mismatch with significantly increased log Q SD (1.29, p less than 0.05) but no increase in shunt (mean 1%). Minor atelectatic areas were noted in three patients, the others displayed no atelectasis at all. Chest dimensions were reduced by no more than 3% during anaesthesia, suggesting an unchanged or only minimally affected functional residual capacity. These findings contrast with those seen in patients with healthy lungs in whom atelectasis and shunt regularly develop during anaesthesia.
Reversal of apnoea by aspiration reflex in anaesthetized cats
Authors: Tomori Z , Benacka R , Donic V , Tkacova R
Published: November 2022

Various flow and timing characteristics of breathing as well as electrocorticographic (ECoG) records were analysed in a model of reversible respiratory failure induced by N2 inhalation in 27 anaesthetized cats. During the first minute of respiratory arrest, nasopharyngeal stimulation by an elastic nylon fibre elicited a typical sniff- or gasp-like aspiration reflex (in 88.8% of cases), whilst similar tracheobronchial irritation evoked a weak cough reaction in one third of cases (34.2%). The aspiration reflex could also be evoked in progressive stages of apnoea characterized by very low and even isoelectric ECoG activity immediately before imminent irreversible respiratory failure, and it could interrupt and replace the periodic gasping sometimes occurring during apnoea. The reflex, comprising powerful inspiration efforts, could be evoked during apnoea many times in succession. Repeated aspiration reflexes alone resulted in recovery from hypoxic apnoea with gradual normalization of ECoG and subsequent restitution of spontaneous breathing even more frequently than it occurred in periodic gasping. Successful resuscitation from hypoxic apnoea by the aspiration reflex in cats suggests that nasopharyngeal stimulation can affect the mechanisms underlying the failure and restitution of breathing at least in some forms of apnoea.
Response to corticosteroids in chronic airflow obstruction: relationship to emphysema and airways collapse
Authors: Weir DC , Gove RI , Robertson AS , Burge PS
Published: November 2022

We have studied the relationship between emphysema and airways collapse, and response to corticosteroids in patients with chronic airflow obstruction. One hundred and seven patients completed a placebo-controlled trial comparing 2 wks treatment with oral prednisolone 40 mg.day-1 to inhaled beclomethasone dipropionate 500 micrograms t.d.s. Response to corticosteroids was defined on the basis of changes in forced expiratory volume in one second (FEV1), and/or forced vital capacity (FVC), and/or mean peak expiratory flow (PEF) after treatment. Patients were categorized as those with physiologically defined emphysema (carbon monoxide transfer coefficient (KCO) less than 70% predicted and total lung capacity greater than 120% predicted), and those with pressure dependent airways collapse on the flow-volume loop (ratio of inspiratory to expiratory flow at 50% vital capacity [I:E50] greater than 10). The response to placebo showed a significant order effect, probably due to a carry-over effect of active treatment of at least 3 wks. Hence, the efficacy of active treatment over placebo in the subgroups defined was assessed by analysis of data generated from the first treatment phase of the trial. The presence or absence of physiologically defined emphysema did not affect the response to oral prednisolone. Inhaled beclomethasone dipropionate, however, was less effective in the emphysema group. Pressure dependent airways collapse did not affect the response to either prednisolone or beclomethasone. However, when data from all three treatment phases were analysed there was no significant difference in the response to either drug in any of the subgroups defined.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo and in vitro inactivation of bovine surfactant by an anti-surfactant monoclonal antibody
Authors: Eijking EP , Strayer DS , van Daal GJ , Tenbrinck R , Merritt TA , Hannappel E , Lachmann B
Published: November 2022

In this study the importance of a low-weight surfactant protein (11 kDa) is demonstrated by selectively blocking this protein with a monoclonal antibody. In adult rats respiratory failure was induced by repeated bronchoalveolar lavage to remove all pulmonary surfactant. It was shown that surfactant mixed with the antibody was not capable of restoring lung function when compared with surfactant alone or surfactant mixed with control serum. Using the pulsating bubble surfactometer, it could be demonstrated that surfactant mixed with this antibody had a significant higher minimum surface tension when compared with surfactant alone, or surfactant mixed with an unrelated mouse immunoglobulin G (IgG). The inhibition of surfactant function by the monoclonal antibody suggests the importance of the 11 kDa protein for normal surfactant function.
Plasma exudation in the airways: mechanisms and function
Authors: Persson CG
Published: November 2022

Inflammatory challenges of tracheobronchial and nasal mucosa produce prompt extravasation or exudation of plasma from the well developed microcirculation just beneath the epithelial base. Plasma exudation is not an exaggeration of the normal capilliary exchange of fluid and solutes but a specific inflammatory response of post-capilliary venules. The exuded plasma may not produce oedema. By a rapid, undirectional, unfiltered and yet non-injurious process, plasma exudates cross the mucosal lining to appear on the airway surface at the site of challenge. In vitro data suggests the possibility that a slightly increased hydrostatic pressure moves the acellular exudate through valve-like openings between epithelial cells. By the venular-mucosal exudation mechanism all the potent protein systems of circulating plasma will operate in respiratory defence on the surface of an intact mucosa. A further inference is that exudative indices obtained from the airway surface quantitatively reflect the intensity and time course of mucosal/submucosal inflammatory processes. Irrespective of which particular cellular mechanism happens to fuel the inflammation. Mucosal exudation of plasma characteristically occurs in health and disease also when there is no airway oedema, no epithelial disruption, and no increased absorbtion ability. However, exuded plasma and its derived peptide mediators potentially contribute to several pathophysical and pathophysiological characteristics of inflammatory airway diseases.
31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure
Authors: Tada H , Kato H , Misawa T , Sasaki F , Hayashi S , Takahashi H , Kutsumi Y , Ishizaki T , Nakai T , Miyabo S
Published: November 2022

The development of 31P-nuclear magnetic resonance (NMR) has enabled direct and non-invasive measurements of muscle metabolism. Serial measurements of the phosphocreatine/inorganic phosphate (PCr/Pi) ratio, which is closely related to the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and pH during and after forearm exercise were performed in 11 patients with chronic lung disease (CLD), nine patients with chronic heart failure (CHF) and eight control subjects. As compared with control subjects, the PCr/Pi ratio in the patients with CLD or CHF was lower during the recovery period and significantly lower at three and 4 min exercise. The pH values after exercise were lower in patients with CLD or CHF compared to control subjects. The PCr/Pi ratio at 4 min after exercise in the patients with CLD or CHF did not correlate with parameters of cardiac function or arterial and mixed venous oxygen tension. The arterial oxygen content and output in patients with CLD and CHF were significantly lower than that of control subjects. Nutritional parameters were not statistically different among the three groups. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with CLD and CHF that are not due to under-nutrition. These may result from reduced arterial oxygen output and, partially, from physical detraining.
Vector analysis in partitioning of inspiratory muscle action in dogs
Authors: Ward ME , Paiva M , Macklem PT
Published: November 2022

We considered the displacements and the pressure changes resulting from isolated contraction of 2 muscles as analogous to 2 vectors and those during simultaneous contraction as resultants. These were resolved into contributing components to calculate the contribution of each muscle group and partition the action of inspiratory muscles. Relative displacements of rib cage (delta RC) and abdomen (delta AB) and changes in transpulmonary (delta PL) and abdominal (delta Pab) pressures were obtained during spontaneous breathing, isolated contraction of rib cage muscle (RCM), diaphragmatic (DI), costal and crural diaphragm and passive inflation in 7 dogs. The diaphragm accounted for 58 +/- 19.8% SD of the chest wall displacement and 90 +/- 6.6% SD of the pressure swings during spontaneous breathing. The costal diaphragm accounted for 61 +/- 28.9% SD of the displacement produced by contraction of the entire diaphragm. Despite wide variability in the action of the diaphragm and its components, all animals breathed close to their relaxation characteristic. We conclude that there are marked differences in the degree of RCM recruitment between dogs in order to prevent chest wall distortions.
Human respiratory mucins
Authors: Lamblin G , Aubert JP , Perini JM , Klein A , Porchet N , Degand P , Roussel P
Published: November 2022

Human respiratory mucins are secreted by goblet cells and mucous glands of the respiratory mucosa. They consist of a broad family of complex glycoproteins with different peptides, or apomucins, corresponding to several genes located on at least three different chromosomes. Glycosylation, the major posttranslational phenomenon, is responsible for about 70-80% of the weight of mucins: it produces an extraordinary diversity of O-glycosidically linked carbohydrate chains which are expressed as several hundreds of different chains in the mucins of a single individual. The variety of mucin peptides and the diversity of carbohydrate chains probably allows many interactions, especially with microorganisms: this may be an essential factor in the defence of the underlying respiratory mucosa.
Six vs twelve cycles for complete responders to chemotherapy in small cell lung cancer: definitive results of a randomized clinical trial. The "Petites Cellules" Group
Authors: Lebeau B , Chastang C , Allard P , Migueres J , Boita F , Fichet D
Published: November 2022

Of 320 patients with small cell lung cancer (SCLC) entered into a clinical trial of chemotherapy between January 1983 and September 1985, 106 patients achieved a complete response. The induction chemotherapy used was lomustine 60 mg.m-2 p.o., cyclophosphamide 1 g.m-2 i.v., doxorubicin 45 mg.m-2 i.v. and etoposide 150 mg.m-2 i.v., every four weeks. Lomustine was only given for the first three cycles. Seventy nine of the 106 patients still in complete response after six chemotherapy cycles were subsequently randomized to receive either six more cycles or no more treatment until relapse. In this group of 79 patients, a difference was shown from the time of inclusion between the 51 patients with limited disease and the 28 patients with disseminated disease, with overall median survivals of 395 and 165 days, respectively, (p = 0.0002). No difference was shown between the two treatment groups: the median survival was 332 days from the time of second randomization with a two year survival rate of 28% for the patients randomized to receive six more cycles and 246 days and 22% for those randomized to receive no more treatment (add 147 days to obtain overall median survival). Continuing chemotherapy for more than six cycles to patients in complete response did not improve survival.
Cough receptor sensitivity and bronchial responsiveness in normal and asthmatic subjects
Authors: Fujimura M , Sakamoto S , Kamio Y , Matsuda T
Published: November 2022

We examined whether airway cough receptor sensitivity correlates to nonspecific bronchial responsiveness. We measured cough threshold, the lowest concentration of inhaled tartaric acid eliciting five or more coughs, and the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20FEV1) in 38 normal and 11 asthmatic subjects. All subjects were nonsmokers. The geometric mean value of PC20FEV1 was 25.7 mg.ml-1 (GSEM1.29) and 0.63 mg.ml-1 (GSEM1.29) and the geometric mean value of the cough threshold was 115 mg.ml-1 (GSEM1.20) and 95.5 mg.ml-1 (GSEM1.35) in normal and asthmatic subjects, respectively. The PC20FEV1 was significantly (p less than 0.01) lower in asthmatics than in normals but the cough threshold did not differ between them. No significant correlation was observed between the cough threshold and the PC20FEV1 in normal subjects or in asthmatics. These results indicate that cough sensitivity does not directly correlate to bronchial responsiveness in normal and asthmatic subjects.
Sleep-related oxygen desaturation and daytime pulmonary haemodynamics in COPD patients
Authors: Levi-Valensi P , Weitzenblum E , Rida Z , Aubry P , Braghiroli A , Donner C , Aprill M , Zielinski J , Wurtemberger G
Published: November 2022

It has been hypothesized that in chronic obstructive pulmonary disease (COPD), sleep-related hypoxaemia could lead to pulmonary hypertension (PH) and cor pulmonale, even in patients with only mild daytime hypoxaemia. We investigated the relationships between sleep variables and daytime pulmonary haemodynamics in 40 COPD patients with daytime arterial oxygen tension (PaO2) between 60-70 mmHg (8-9.3 kPa). Patients were considered as desaturators if they spent at least 30% of the sleep recording time with a transcutaneous O2 saturation (StcO2) less than 90%. Daytime arterial blood gases and pulmonary volumes could not discriminate desaturators "D" (n = 18) from non-desaturators "ND" (n = 22), but awake baseline StcO2, measured just prior to the onset of sleep, was lower in group D. Pulmonary artery mean pressure was significantly higher in group D (19.1 +/- 4.7 vs 16.8 +/- 1.9 mmHg, p less than 0.05) and all patients with PH (6 out of 40) belonged to group D. PH was observed in 6 of the 15 patients whose mean nocturnal StcO2 was less than 90% but in none of the 25 with a mean nocturnal StcO2 greater than 90%. The PH patients (n = 6), all desaturators, differed from the desaturators with no PH (n = 12), and from ND (n = 22) in having higher numbers of desaturation dips, longer durations of dips, and lower mean nocturnal arterial oxygen saturation (SaO2). We conclude that a causal relation between nocturnal desaturation and permanent PH is very likely. Further studies are needed to see whether oxygen therapy can prevent PH in these patients.
Effect of hyposensitization upon the immediate and late asthmatic reaction and upon histamine reactivity in patients allergic to house dust mite (Dermatophagoides pteronyssinus)
Authors: Van Bever HP , Stevens WJ
Published: November 2022

The effect of hyposensitization (HS) upon the allergen evoked immediate asthmatic reaction (IAR), late asthmatic reaction (LAR) and upon bronchial reactivity towards histamine was examined. Eighteen young asthmatic patients were studied using a double-blind, placebo-controlled design. All were allergic to house dust mite (HDM) and demonstrated an IAR and a LAR after bronchial provocation with HDM. Furthermore, all, except one child, demonstrated bronchial hyperreactivity towards histamine (median provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) histamine = 0.19 mg.ml-1, range: 0.02-8 mg.ml-1). The subjects were randomly divided into two groups to receive HDM or placebo injections during one year. After the one year period, the IAR was less severe in the subjects who received HDM injections (p = 0.02), while this reduction was not observed in the subjects who received placebo injections. Also, in the HDM group a small but significant increase of the median PD20 HDM was observed (p = 0.04). Furthermore, the LAR was less severe in the subjects who received HDM injections (p = 0.02), while the subjects who received placebo injections showed the same severity of LAR after one year (p = 0.44). Histamine reactivity did not change after HDM injections or after placebo injections. Thus, HS reduces the severity of the IAR and LAR without any change in histamine reactivity.