bluuebunny/crossref_metadata_2025 huggingface dataset:
BAL lymphocyte activation antigens and diffusing capacity are related in mild to moderate pulmonary sarcoidosis
Authors: Xaubet A , Agusti C , Roca J , Picado C , Rodriguez-Roisin R
Published: November 2022

To investigate the relationship [corrected] between immunocytological features of bronchoalveolar lavage (BAL) and clinical indices in sarcoidosis, we studied the lymphocyte subsets, as well as the expression of human leucocyte antigen-DR (HLA-DR) and interleukin 2 receptor (IL-2R) antigens in BAL lymphocytes. We studied 16 patients with untreated sarcoidosis and 12 control subjects. We found significantly higher absolute numbers of lymphocytes bearing the IL-2R antigen in sarcoidosis. A stronger difference between groups was observed in both the percentage and absolute numbers of HLA-DR+ lymphocytes. We also found a moderate but significant correlation between the number of lymphocytes expressing the activation antigens and single breath carbon monoxide diffusing capacity in patients with sarcoidosis: DLCO vs HLA-DR+ lymphocytes (r = -0.60); DLCO vs IL-2R+ lymphocytes (r = -0.62); carbon monoxide transfer coefficient (KCO vs HLA-DR+ lymphocytes (r = -0.53); and KCO vs IL-2R+ lymphocytes (r = -0.58). Our results suggest that the reduction in diffusing capacity, expressed as either DLCO or KCO, results from the severity of alveolitis in mild to moderate sarcoidosis.
Tachykinin receptors and airway pathophysiology
Authors: Maggi CA
Published: November 2022

The mammalian tachykinins (TKs), substance P and neurokinin A, are present in sensory nerve fibres in the upper and lower airways of various mammalian species, including humans. TKs are released from these afferent nerves in an "efferent" mode at peripheral level, especially in response to irritant stimuli. TKs exert a variety of biological effects (bronchoconstriction, plasma protein extravasation, stimulation of mucus secretion), collectively known as "neurogenic inflammation", and this process is thought to be of potential pathogenic relevance for various airway diseases. The recent development of potent and selective TK receptor antagonists on the one hand provides important new tools for the understanding of basic airway physiology and pathophysiology and, on the other, opens new possibilities for therapy of airway diseases.
Chromosome typing in lymphangioleiomyomatosis of the lung with and without tuberous sclerosis
Authors: Popper HH , Gamperl R , Pongratz MG , Kullnig P , Juttner-Smolle FM , Pfragner R
Published: November 2022

Two cases of lymphangioleiomyomatosis (LLM) of the lungs are compared, one with tuberous sclerosis and the other representing an isolated lung involvement. An increased frequency of complex chromosomal rearrangements was found in peripheral lymphocytes of the patient with tuberous sclerosis, in comparison to the patient with isolated lymphangioleiomyomatosis. Telomeric associations were found in cultured pulmonary smooth muscle cells from the patient with isolated LLM.
Leucocyte elastase-mediated release of von Willebrand factor from cultured endothelial cells
Authors: Chignard M , Balloy V , Renesto P
Published: November 2022

The aim of this study was to investigate a possible activation of human endothelial cells in monolayer culture by a purified neutrophil-derived proteinase, i.e. elastase. Cells were isolated from human umbilical cord veins, and incubated either in primary culture or after two passages, in the presence of various concentrations of this proteinase. Although a lack of prostacyclin formation was noted, elastase induced a large release of von Willebrand factor (vWf) in a concentration-dependent manner. Thus, upon incubation with 1 microgram.ml-1 elastase for 30 min, 70 mU.ml-1 vWf were detected in the incubation medium, as compared to 5 mU.ml-1 for control. Using cells in primary culture, a fivefold higher concentration of vWf was recovered following incubation with 10 micrograms.ml-1 elastase than with 0.5 IU.ml-1 thrombin. This effect was linked to the enzymatic activity of elastase and not to its cationic charge, as deduced from the inhibition by eglin C, and the lack of effect of the phenylmethylsulphonyl fluoride (PMSF) treated proteinase. We conclude that vWf release was not due to cell activation, since cytoplasmic calcium mobilization was absent, and inhibition of protein kinase C did not modify the response. In fact, this release was the consequence of cell damage, since concentrations of vWf recovered correlated with cell lysis. These results support the hypothesis that the high level of plasma vWf in patients with sepsis or adult respiratory distress syndrome could result from damage to the endothelial cells by elastase released from activated neutrophils.
Clearance of inhaled 99mTc-DTPA predicts the clinical course of fibrosing alveolitis
Authors: Wells AU , Hansell DM , Harrison NK , Lawrence R , Black CM , du Bois RM
Published: November 2022

The aim of this study was to determine whether the speed of technetium-labelled diethylene-triamine-pentacetate (99mTc-DTPA) clearance from the lung is predictive of disease progression in fibrosing alveolitis, as judged by changes in respiratory function tests. 82 nonsmoking patients with fibrosing alveolitis were studied (progressive systemic sclerosis, n = 53; lone cryptogenic fibrosing alveolitis, n = 29). Normal 99mTc-DTPA clearance at initial measurement predicted stable disease; rapid 99mTc-DTPA clearance identified patients at risk of deterioration. Repeat measurement of clearance, approximately 12 months later, enabled the definition of a subgroup at higher risk, with persistently abnormal 99mTc-DTPA clearance, and a smaller subgroup in whom reversion of clearance to normal was associated with a sustained improvement in respiratory function indices. These findings were not attributable to differences in treatment between subgroups. We conclude that the speed of 99mTc-DTPA clearance discriminates between stable and progressive disease in fibrosing alveolitis.
Serial pulmonary function tests in the diagnosis of P. carinii pneumonia
Authors: Mitchell DM , Fleming J , Harris  , Shaw RJ
Published: November 2022

The predictive value of serial versus isolated measurements of transfer factor for carbon monoxide (TLCO) in the diagnosis of pneumocystis carinii pneumonia (PCP) in a cohort of 474 HIV-1 seropositive patients, with all stages of HIV disease, was evaluated. Two groups of patients were studied, one group with serial lung function measurements (Group 1) and another with only a single set of measurements (Group 2). During the study period 118 patients performing serial tests developed a respiratory illness of which 58 were performing monthly and 60 three monthly measurements of lung function (Group 1). In 36 patients from Group 1, where PCP was diagnosed, monthly lung function tests showed a decrease in TLCO from 68% (+/- 3.2) (SEM), (8 weeks prior to illness), to 44% (+/- 2.5) predicted normal at presentation, whereas in 22 patients who did not have PCP, TLCO fell from 71% (+/- 4.5) to 57% (+/- 3.1). TLCO was thus reduced to lower values in these with PCP than in those without PCP (p < 0.05). A fall of TLCO of 5% from initial values when used as predictive for presence of PCP had a sensitivity of 75% and a specificty of 28% (positive predictive value 56%; negative predictive value 48%). TLCO was < 70% predicted in 72/78 patients with PCP who performed only single lung function tests (Group 2), which gave a sensitivity of 92% and a specificity of 71% as a diagnostic test for PCP when compared with the cohort as a whole. The positive predictive value was 34%, negative predictive value was 98%.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in respiratory symptoms and airway hyperresponsiveness after 27 years in a population-based sample of school children
Authors: de Gooijer A , Brand PL , Gerritsen J , Koeter GH , Postma DS , Knol K
Published: November 2022

We wanted to test the hypothesis that childhood airway hyperresponsiveness, even in the absence of respiratory symptoms, is a risk factor for respiratory disease in adulthood. In a childhood survey of 1963, three groups of 20 children aged 8-11 yrs, were selected from a population sample: 1) a group with recurrent respiratory symptoms (symptomatic group); 2) a group with no symptoms but a positive family history of atopy; and 3) a control group. All children completed assessment of symptoms, atopy, lung function, and airway hyperresponsiveness. At the adulthood survey 27 yrs later, 85% of the original sample were reinvestigated. Only 10 out of 19 subjects (53%) of the original symptomatic group still had symptoms. The significant difference of forced expiratory volume in one second (FEV1) % predicted in childhood between the symptomatic and the control group had disappeared. The prevalence of airway hyperresponsiveness had decreased in all groups. In asymptomatic hyperresponders it had normalized at adult age. The asymptomatic hyperresponders in childhood had lower levels of lung function, both in childhood and in adulthood. In univariate and multivariate analyses, respiratory symptoms at adult age were related to childhood atopy. Results suggest that childhood atopy is a risk factor for respiratory symptoms in young adulthood, but that mild childhood airway hyperresponsiveness is not.
Environmental pleural plaques in an asbestos exposed population of northeast Corsica
Authors: Rey F , Boutin C , Steinbauer J , Viallat  , Alessandroni P , Jutisz P , Di Giambattista D , Billon-Galland MA , Hereng P , Dumortier P , et al.
Published: November 2022

The purpose of this study was to determine whether the inhabitants of villages environmentally exposed to asbestos, in northeast Corsica, had a higher incidence of pleural plaques. X-rays were obtained from subjects aged over 50 yrs, with no occupational exposure to asbestos or history of pleural disease, in one village exposed to asbestos, Murato, and a nonexposed, control village, Vezzani. In addition, the mineral content of the air and parietal pleura of animals in the exposed zone was studied, using transmission electron microscopy. The incidence of bilateral pleural plaques in the exposed population was 41%, as compared to 7.5% in the nonexposed population (p < 0.00001). The levels of airborne tremolite were higher in Murato (6-72 ng.m-3) than in Vezzani (< 1 ng.m-3), but chrysotile levels were similar. Significant numbers of chrysotile and tremolite fibres were identified in the parietal pleura of animals from the exposed village. This study confirms the well-known correlation between bilateral pleural plaques and environmental exposure to low levels of asbestos.
The contribution of respiratory function tests to clinical diagnosis
Authors: Laszlo G , Lance GN , Lewis GT , Hughes AO
Published: November 2022

The purpose of this study was to investigate the amount of diagnostic information contained in a set of routine lung function studies and to attempt to determine which tests could be omitted without significant loss of discrimination. Cluster analysis was performed on a set of physiological and questionnaire data, collected prospectively in 1,542 male patients, referred consecutively for measurement of forced expired volumes, static lung volumes and measurements of the transfer factor for carbon monoxide. A respiratory questionnaire was completed for each patient. A physician assigned the patients to a rigorously defined diagnostic category, based on supporting clinical information, as well as pulmonary function, apart from 241 patients with unusual diagnoses and those in whom the criteria did not apply satisfactorily. This diagnosis was never included as a classification variable. Basing the classification on three independent measurements, total lung capacity, the ratio of forced expiratory volume in one second (FEV1) to vital capacity, and the transfer factor for carbon monoxide, the computer generated six groups: one normal, one showing an isolated gas exchange defect, and four with varying degrees of restriction and obstruction. This classification performed well in separating the patients with the clinical diagnoses of chronic airflow obstruction, bronchial asthma and interstitial lung disease from those with ischaemic and valvular heart disease and other miscellaneous disorders. Omitting total lung capacity resulted in some loss of specificity, but valid information was still obtained. The inclusion of all the static and dynamic lung volumes and of carbon monoxide transfer coefficient made little difference.(ABSTRACT TRUNCATED AT 250 WORDS)
An evaluation of P0.1 measured in mouth and oesophagus, during carbon dioxide rebreathing in COPD
Authors: Elliott MW , Mulvey DA , Green M , Moxham J
Published: November 2022

The pressure generated 100 ms after the onset of an occluded inspiratory effort (P0.1) is advocated and used as a measure of respiratory centre drive. We have re-examined P0.1, measured simultaneously in the mouth (Pmo0.1) and the oesophagus (Poes0.1), during carbon dioxide rebreathing, in eight patients with severe chronic obstructive pulmonary disease, to see whether either indicates central respiratory drive. Pmo0.1 was identical to Poes0.1 in 4 out of 61, greater than Poes0.1 in 18 out of 61, and less than Poes0.1 in 39 out of 61 measurements (overall Poes0.1-Pmo0.1, median +0.075, range -0.175 to +1.01 kPa). Within a rebreathing run in an individual patient, there was considerable variability in the relationship Pmo0.1/Poes0.1 (0.89 +/- 0.24), coefficient of variation (CoV%) 14.4 +/- 3.7%), in the end-expiratory oesophageal pressure (0.7 +/- 0.54 kPa, CoV% 105 +/- 106%), and in the time delay between the onset of a fall in oesophageal pressure (Poes) from the end-expiratory level to the beginning of inspiration, defined as starting when mouth pressure (Pmo) fell below atmospheric pressure (129 +/- 25 ms, CoV% 22.5 +/- 5.3%). We conclude that the problem of determining the true onset of inspiratory muscle activity from pressure data, and the likelihood that breaths are taken from different lung volumes, make it unlikely that Poes0.1 accurately represents central respiratory drive during rebreathing in chronic obstructive pulmonary disease. Furthermore, Pmo0.1 differed from Poes0.1 during rebreathing, and their relationship was not constant, so that Pmo0.1 is even less likely to be a useful reflection of central nervous system output or respiratory centre drive in such patients.
Comparison of pressure and volume preset nasal ventilator systems in stable chronic respiratory failure
Authors: Meecham Jones DJ , Wedzicha JA
Published: November 2022

Nasal intermittent positive pressure ventilation (NIPPV) has been widely used in the treatment of chronic respiratory disease. Ventilators may be volume or pressure preset; each type has theoretical advantages, but to date there has been no formal comparison. We wanted to assess the efficacy on blood gas changes that may be achieved and overall acceptability of four nasal ventilators (two pressure preset: Respironics bilevel positive airway pressure (BiPAP) and the Thomas NIPPY; and two volume preset: BromptonPac and Monnal-D) in patients with stable chronic respiratory failure. Median age was 59 yrs (range 48-71 yrs), mean (SD) arterial oxygen tension (PaO2) 7.16 (0.21) kPa, arterial carbon dioxide tension (PaCO2) 7.02 (0.35) kPa, forced expiratory volume in one second (FEV1) 0.76 (0.24) l, and forced vital capacity (FVC) 1.58 (0.49) l. All had previously used NIPPV. There were significant changes in blood gases at 2 h with each ventilator: mean change (95% confidence interval); BiPAP PaO2 +1.52 (0.95-2.09) kPa, PaCO2-1.04 (1.55-0.54) kPa; NIPPY PaO2 +1.63 (0.85-2.41) kPa, PaCO2, -1.1 (1.86-0.34) kPa; BromptonPac PaO2 +1.22 (0.75-1.67) kPa, PaCO2 -1.14 (1.52-0.76) kPa; Monnal-D PaO2 +1.14 (0.42-1.84) kPa, PaCO2 -1.19 (2.14-0.23) kPa. Analysis of variance showed no significant differences in the efficacy of volume or pressure preset equipment, and all ventilators proved equally acceptable to the patients studied. We conclude that all four of the volume or pressure preset ventilators examined are suitable for the delivery of nasal intermittent positive pressure ventilation in patients with stable chronic respiratory failure.
Ventilatory pattern during bronchial histamine challenge in asthmatics
Authors: Stromberg NO , Gustafsson PM
Published: November 2022

We wanted to investigate whether asthmatic subjects change their ventilatory pattern consistently when forced expiratory volume in one second (FEV1) has declined by at least 20% during bronchial histamine challenge, in order to assess whether respiratory pattern analysis can be used to monitor bronchial obstruction continuously. Histamine challenge was performed twice within a four week period, in eight asthmatic teenagers. Respiratory inductive plethysmography (RIP) was used for respiratory pattern evaluation, whilst the patients breathed on a mouthpiece attached to a pneumo-tachometer (PTM) whilst wearing a noseclip (first histamine challenge), and during natural breathing (second HiCh). End-tidal carbon dioxide tension (PETCO2) was measured on both occasions. During the second histamine challenge, four of the eight patients responded with a 72% (mean) increase in minute ventilation (VE), an 80% increase in mean inspiratory flow (VI), and a 20% decrease in PETCO2. VE and VI were unchanged, or tended to decrease, among the other four patients (ventilatory nonresponders). Neither provocative dose producing a 20% fall in FEV1 (PD20) to histamine nor the magnitude of the fall in FEV1 differed between ventilatory responders and nonresponders. The ventilatory response to inhaled histamine was abolished when breathing through a PTM. Histamine induced bronchospasm is not uniformly reflected in the breathing pattern. Hyperventilation during histamine challenge might be the consequence of vagal airway receptor activation. Respiratory pattern analysis is not a feasible way to monitor bronchial obstruction during histamine challenge.
Effect of furosemide on the response of laryngeal receptors to low-chloride solutions
Authors: Sant'Ambrogio FB , Sant'Ambrogio G , Anderson JW
Published: November 2022

Laryngeal irritant receptors are stimulated by water and solutions lacking chloride ions, such as isotonic dextrose. It has been reported that furosemide (frusemide) reduces cough evoked by inhalation of low-chloride solutions. We studied the effect of furosemide on the response of laryngeal receptors to isotonic dextrose. Experiments were performed on nine dogs anaesthetized, spontaneously breathing through a tracheostomy, and with the upper airway functionally isolated. We recorded the activity of 13 laryngeal irritant receptors. Isotonic dextrose (4 ml) was instilled into the laryngeal lumen, before and after administration of a furosemide solution (3.75 mg.ml-1) into the upper airway. Before furosemide, dextrose increased the activity of the 13 receptors from 1.0 +/- 0.5 to 25.0 +/- 3.5 impulses (imp).s-1 (average discharge in the first 10 s of activation) and, 1-2 min after furosemide, from 0.3 +/- 0.2 to 13.4 +/- 3.2 imp.s-1; the difference between the stimulation by dextrose before and after furosemide was statistically significant. In contrast, the response to distilled water of four respiratory-modulated mechano-receptors (known to be activated by low-osmolality solutions) was not modified by furosemide. These results suggest that the furosemide-mediated inhibition of cough induced by inhalation of low-chloride solutions is, at least in part, due to the inhibitory effect of this substance on irritant receptor stimulation.
Total respiratory impedance and early emphysema
Authors: Govaerts E , Demedts M , Van de Woestijne KP
Published: November 2022

It can be postulated that patients in early stages of pulmonary emphysema have normal values of total respiratory resistance and reactance. The purpose of this study was to investigate whether pulmonary emphysema, detected functionally by a decrease of the single breath diffusing capacity (DLCO) by at least 25% of predicted, and an increase of the static lung compliance (CLst) by at least 50% of predicted, can be accompanied by normal values of respiratory resistance (Rrs) and reactance (Xrs), measured between 2 and 24 Hz by the forced oscillation technique. In a prospective study, we determined CLst in 26 patients, who had been selected on the basis of normal values of Rrs and Xrs, and a DLCO of less than 75% of predicted. In 17 of these patients, CLst was more than 150% of predicted. Since there were only minor abnormalities on routine lung function tests and chest X-ray, it is likely that these patients presented early emphysema. In the nine other patients, CLst was within normal limits: four suffered from interstitial lung disease; the remaining five were probably in a preliminary stage of early emphysema. In conclusion, early emphysema should systematically be considered as the first diagnosis in patients with normal values of Rrs and Xrs, and a decrease of DLCO. Onset of interstitial lung disease is a possible alternative.
Obliterative bronchiolitis with atypical features: CT scan and necropsy findings
Authors: Noble MI , Fox B , Horsfield K , Gordon I , Heaton R , Seed WA , Guz A
Published: November 2022

We describe the natural history of cryptogenic bronchiolitis obliterans in a patient followed for 24 yrs with serial pulmonary function tests and radiology. Severe, progressive airway obstruction developed, with overinflation but preservation of KCO. There was progressive hypoxaemia, which worsened on exertion; hypercapnoea was modest until late in the illness. Neither bronchodilators nor steroids were effective. The chest radiograph remained normal; CT showed irregular areas of low attenuation peripherally throughout the lungs, with Hounsfield numbers typical of emphysema, but no bullae. Postmortem studies included histology and quantitative studies of a corrosion cast of one lung. They showed marked airway narrowing at all levels, with pruning of peripheral branches, mucus plugging, and some emphysema. The case illustrates that cryptogenic bronchiolitis obliterans may be chronic and difficult to distinguish clinically or by investigation from other forms of chronic obstructive airways disease, particularly emphysema.
Abnormal alveolar macrophage populations in bone marrow transplant recipients with pneumonitis
Authors: Milburn HJ , Prentice HG , Poulter LW
Published: November 2022

The purpose of this investigation was to determine whether there is any relationship between different subsets of alveolar macrophages and type of infection or survival from interstitial pneumonitis following bone marrow transplantation (BMT). The population of alveolar macrophages found in bronchoalveolar lavage fluid (BALF) from 16 BMT recipients with 19 episodes of interstitial pneumonitis was investigated, using immunocytochemical methods. Results were compared with those from seven normal volunteers. The results showed that patients with pneumonitis had significantly higher numbers of total cells in BALF than normals but reduced proportions of macrophages, although the absolute numbers were unchanged. Of the cells present which were morphologically macrophages, there were raised proportions of both RFD1+ cells (interdigitating cells) and RFD7+ cells (mature macrophages) in patients compared with normals, but expansion of these two subsets could be explained, in part, by a significant increase in cells positive for both markers (42% in patients compared with 9% in normals). Proportions of cells with the monocyte phenotype (CD14+, UCHM1) were also significantly raised in patients with pneumonitis (17% compared with 6% in normals). These patients, however, had significantly reduced proportions of macrophage-like cells which were positive for the DR antigen (Class II major histocompatibility complex (MHC) antigen) (47% compared with 88% in normals), and this abnormality was greater still in patients who died from pneumonitis (40%) compared with those who survived (52%). The results of this study indicate a breakdown of local immunoregulation, thus contributing to the high incidence of, and mortality from, opportunistic pulmonary infections in this group.
Determination of peak expiratory flow
Authors: Kano S , Burton DL , Lanteri CJ , Sly PD
Published: November 2022

It is still unknown whether peak expiratory flow (PEF) is determined by "wave speed" flow limitation in the airways. To investigate the influences of airway mechanical properties on PEF, five healthy adults performed maximal forced expiratory effort (MFEE) manoeuvres, in the standard manner and following breathholds at total lung capacity (TLC) of 2 s and 10 s. Oesophageal pressure (Poes) was measured as an index of respiratory effort. Subjects also performed a MFEE following a 10 s breathhold during which intrathoracic pressure was voluntarily raised by a Valsalva manoeuvre, which would increase transmural pressure and cross-sectional area of the extrathoracic airway. Additional MFEEs were performed with the neck fully flexed and extended, to change longitudinal tracheal tension. In separate studies, PEF was measured with a spirometer and with a pneumotachograph. Breathholds at TLC (2 s and 10 s), and neck flexion reduced PEF by a mean of 9.8% (SD 2.9%), 9.6% (SD 1.6%), and 8.7% (SD 2.8%), respectively, when measured with the spirometer. The same pattern of results was seen when measured with the pneumotachograph. These reductions occurred despite similar respiratory effort. Voluntarily raising intrathoracic pressure during a 10 s breathhold did not reverse a fall in PEF. MFEE manoeuvre with neck extension did not result in an increase in PEF, the group mean % changes being -3.0% (SD 5.0%). We conclude that these results do not allow the hypothesis that "wave-speed" (Vws) is reached at PEF to be rejected. A breathhold at TLC could increase airway wall compliance by allowing stress-relaxation of the airway, thus reducing the "Vws" achievable.
Relationship between exercise capacity and the severity of emphysema as determined by high resolution CT
Authors: Wakayama K , Kurihara N , Fujimoto S , Hata M , Takeda T
Published: November 2022

We investigated the relationship between exercise capacity or exercise-induced hypoxaemia and the severity of pulmonary emphysema in 20 patients with pulmonary emphysema. The patients underwent pulmonary function tests, high resolution computed tomography and incremental treadmill exercise testing. Computed tomography scans were obtained at four levels in the lungs, and emphysema scores were determined by the visual assessment of low attenuation areas as a measure of the severity of parenchymal destruction. The emphysema score correlated significantly with diffusing capacity (r = -0.69) in the pulmonary function tests. Among the exercise test parameters, the emphysema score correlated significantly with the total distance walked (r = -0.74), with maximal oxygen consumption (VO2max) (r = -0.77), with arterial oxygen tension (PaO2) at rest (r = -0.50) and at the maximum workload (r = -0.58), and with the decrement of arterial oxygen tension per litre of oxygen consumed (r = -0.64). These results suggest that exercise capacity and exercise-induced hypoxaemia are related to the extent of destruction of lung parenchyma in patients with pulmonary emphysema.
Increased amount of nitric oxide in exhaled air of asthmatics
Authors: Alving K , Weitzberg E , Lundberg JM
Published: November 2022

The presence of nitric oxide (NO) in the exhaled air of humans has recently been described. We wanted to assess at what level exhaled NO originates in normal airways, and to determine whether airway inflammation induces changes in the levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence technique during normal tidal breathing through the nose or mouth, with a detection limit of 1 part per billion (ppb). Twelve control subjects were compared to eight patients with mild atopic asthma and rhinitis caused by occupational allergen. In control subjects, the major part of NO in exhaled air (up to 30 ppb) seemed to originate in the nasal airways, with only minor contribution from the lower airways and the oral cavity. However, in mild asthmatics, the level of exhaled NO during oral breathing, indicating the involvement of the lower airways, was increased 2-3 fold. Since increased production of NO in the lower airways may involve activated macrophages or neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing bronchial inflammation, at least when involving inducible NO synthase.
Acute interstitial pneumonitis induced by carbamazepine
Authors: Takahashi N , Aizawa H , Takata S , Matsumoto K , Koto H , Inoue H , Hara N
Published: November 2022

A 62 year old man treated with carbamazepine for 3 months developed eczema and acute interstitial pneumonitis. A lymphocyte-stimulation test was reactive to carbamazepine. Withdrawal of the drug resulted in prompt improvement. Only 10 cases of this type of drug-induced lung disease have previously been reported.
Regulation of cytokine secretion by cystic fibrosis airway epithelial cells
Authors: Ruef C , Jefferson DM , Schlegel-Haueter SE , Suter S
Published: November 2022

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.
Quality-of-life in a long-term multicentre trial in chronic nonspecific lung disease: assessment at baseline. The Dutch CNSLD Study Group
Authors: Kaptein AA , Brand PL , Dekker FW , Kerstjens HA , Postma DS , Sluiter HJ
Published: November 2022

Quality-of-life (QOL) in patients with respiratory illness is a topic of increasing interest to clinicians and researchers. In a multicentre trial, which studies the long-term effects of three medication regimens (beta-agonist plus either placebo, anticholinergic agent or corticosteroid, all by inhalation) in patients with chronic nonspecific lung disease ((CNSLD): asthma and chronic obstructive pulmonary disease (COPD)), quality-of-life was included as an additional outcome measure. We wanted to provide a baseline assessment of quality-of-life in 274 adult patients with a mild to moderate degree of CNSLD. Quality-of-life was measured using a set of six standardized tests: Anxiety, Depression and Sleep Disorders, Optimism and Stigma, and Activities of Daily Living were assessed via scales with adequate validity and reliability, as established in previous work in Dutch patients with CNSLD. We found that quality-of-life was mildly impaired in these patients. Although differences with a reference group were present throughout, these were not significant, probably due to selection of relatively young, clinically stable, and highly motivated patients for our study. Quality-of-life scores showed higher correlation coefficients (0.20 < r < 0.38) to symptom scores than did results of pulmonary function tests (r < 0.015). In logistic regression models, absence from work and hospitalizations due to CNSLD were partly determined by quality-of-life scores.(ABSTRACT TRUNCATED AT 250 WORDS)
Expired air temperature at the mouth during a maximal forced expiratory manoeuvre
Authors: Madan I , Bright P , Miller MR
Published: November 2022

We have studied the temperature of expired air during a maximal forced expiratory manoeuvre, because this has not previously been fully investigated and it will influence how flow and volume recording devices should be calibrated and used. Temperature was recorded with a fine thermocouple, the response time of which was determined at various gas velocities and for which a correction was made. Recordings during maximal forced expiratory manoeuvres were made on 12 normal subjects and 12 subjects with chronic airflow limitation. The thermocouple was placed in the mouthpiece, so that it was at the level of the lips during a blow. In the normal subjects, the effect of differing inhalation protocols was also determined. In the normal subjects, the mean temperature was 33.6 degrees C at peak expiratory flow (PEF), and 34.4 degrees C at 75% forced vital capacity (FVC), but fell to 33.4 degrees C at FVC. In the subjects with chronic airflow limitation, the temperature was constant at 35.0 degrees C from PEF up to 50% FVC, being significantly higher than in the normals, and fell to 33.5 degrees C at FVC. Expired air temperature up to 50% FVC was significantly negatively correlated with absolute PEF, forced expiratory volume in one second (FEV1) and FVC. In the normals, a slow inhalation through the nose raised the expired temperature by almost 1 degree C throughout the blow, whereas inhaling air at 6 degrees C did not affect expired air temperature. The expired air temperature can vary by up to 3 degrees C between individual subjects, and it is influenced by the route of inhalation and the inspired volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Brucella haemorrhagic pleural effusion
Authors: Papiris SA , Maniati MA , Haritou A , Constantopoulous SH
Published: November 2022

Brucella melitensis (BM) is a rare respiratory pathogen. The lungs are usually affected in the subacute and chronic course of the disease, when pleurisy, empyema, hilar adenopathy, pneumonia and lung abscess have been described. We present a patient with BM haemorrhagic pleural effusion, with low pH, low glucose and positive pleural fluid cultures. Brucellosis should be considered in the differential diagnosis of patients with long-standing pleural effusions of unknown aetiology.
Failing the four-gamete test enables exact phasing: the Corners’ Algorithm
Authors: Gomez-Raya Luis , Rauw Wendy M.
Published: November 2022

Background

Failing the four-gamete test for two polymorphic DNA markers is an indication that two or three rather than four haplotypes segregate in the population. The objective of this paper is to show that when just three haplotypes are segregating, all three haplotypes can be fully and unambiguously phase-resolved.

Theory and methods

The Corners’ Algorithm tests the four corners in a 3 × 3 table of two-locus genotypes. If one of the four corners is filled with zeroes, then the missing haplotype is identified and the phases of all three haplotypes can be unambiguously resolved for all individuals. Three applications of this method are proposed when the four-gamete test fails: (1) direct estimation of linkage disequilibrium (LD), (2) haplotype-based genome-wide association studies (GWAS) of three haplotypes (single-marker GWAS tests for two out of three haplotypes only), and (3) haplotyping of chromosomal regions that are comprised of pairs of single nucleotide polymorphisms (SNPs) that consist of just three haplotypes. An example based on 435 sows with performance records for total number of piglets born is used to illustrate the methods.

Results

Of 20,339 SNPs, approximately 50% of the pairs of flanking SNPs failed the four-gamete test. For those, the expectation maximization (EM) algorithm gave the same results. The average of the absolute value of the difference inr2between flanking SNPs across the genome between the two methods was 0.00082. Single-marker GWAS (using two of three haplotypes) detected significant associations for total number of piglets born on chromosomes 1, 2, 6, 9, 10, 12, 13, 14, 15, and 18. Haplotype-based GWAS using the third haplotype resolved with the Corners’ Algorithm detected additional significant associations for total number of piglets born on chromosomes 2, 5, 10, 13, 14, 15, and 18. Estimated substitution effects ranged from 0.40 to 1.35 piglets. Haplotyping of chromosomal regions that failed the four-gamete test for any pair of SNPs covered 961 Mb out of the 2249 Mb by the SNP array.

Conclusions

The Corner’s Algorithm allows to fully phase haplotypes when the four-gamete test fails. Longer haplotypes in chromosomal regions in which the four-gamete test fails for any pair of SNPs can be used as a multi-allelic marker with increased polymorphism information content.
Early changes in gene expression profiles in AML patients during induction chemotherapy
Authors: Jakobsen Ingrid , Sundkvist Max , Björn Niclas , Gréen Henrik , Lotfi Kourosh
Published: November 2022

Background

Elucidation of the genetic mechanisms underlying treatment response to standard induction chemotherapy in AML patients is warranted, in order to aid in risk-adapted treatment decisions as novel treatments are emerging. In this pilot study, we explored the treatment-induced expression patterns in a small cohort of AML patients by analyzing differential gene expression (DGE) over the first 2 days of induction chemotherapy.

Methods

Blood samples were collected from ten AML patients at baseline (before treatment initiation) and during the first 2 days of treatment (Day 1; approximately 24 h, and Day 2; approximately 48 h after treatment initiation, respectively) and RNA was extracted for subsequent RNA sequencing. DGE between time points were assessed by pairwise analysis using the R package edgeR version 3.18.1 in all patients as well as in relation to treatment response (complete remission, CR, vs non-complete remission, nCR). Ingenuity Pathway Analysis (Qiagen) software was used for pathway analysis and visualization.

Results

After initial data quality control, two patients were excluded from further analysis, resulting in a final cohort of eight patients with data from all three timepoints. DGE analysis demonstrated activation of pathways with genes directly or indirectly associated with NF-κB signaling. Significant activation of the NF-κB pathway was seen in 50% of the patients 2 days after treatment start, while iNOS pathway effects could be identified already after 1 day. nCR patients displayed activation of pathways associated with cell cycle progression, oncogenesis and anti-apoptotic behavior, including the STAT3 pathway and Salvage pathways of pyrimidine ribonucleotides. Notably, a significant induction of cytidine deaminase, an enzyme responsible for the deamination of Ara-C, could be observed between baseline and Day 2 in the nCR patients but not in patients achieving CR.

Conclusions

In conclusion, we show that time-course analysis of gene expression represents a feasible approach to identify relevant pathways affected by standard induction chemotherapy in AML patients. This poses as a potential method for elucidating new drug targets and biomarkers for categorizing disease aggressiveness and evaluating treatment response. However, more studies on larger cohorts are warranted to elucidate the transcriptional basis for drug response.
Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients
Authors: Wakai Haruki , Abe Natsumi , Tokuda Touno , Yamanaka Rika , Ebihara Satoshi , Izumaru Kensuke , Ishii Daisuke , Hyodo Toru , Yoshida Kazunari
Published: November 2022

Objectives

There is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined.

Methods

Baseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients.

Results

The maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL.

Conclusions

The presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.
Why do men who have sex with men practice condomless sex? A systematic review and meta-synthesis
Authors: Shen Yan , Zhang Ci , Valimaki Maritta A. , Qian Hanzhu , Mohammadi Leila , Chi Yuanyuan , Li Xianhong
Published: November 2022

Background

Despite a large amount of behavioral interventions to reduce human immunodeficiency virus (HIV)-related high-risk sexual behaviors, consistent condom use remains suboptimal among men who have sex with men (MSM). However, current databases are lack of synthesized evidence to explain why MSM practiced condomless sex.

Objective

Our study aims to conduct a systematic review and meta-synthesis of 39 eligible qualitative studies to explore the barriers to condom use among MSM.

Methods

A systematic review and meta-synthesis of qualitative studies (1994–2021). On March 4, 2021, a comprehensive search was conducted in 14 electronic databases. The study was conducted based on the Joanna Briggs Institute’s recommendations.

Results

Thematic analysis produced six synthesized themes, which were classified into three levels according to the Social-ecology Model. Individual level barriers to condom use included physical discomfort, lack of HIV/STI-related knowledge and substance use; interpersonal-level barrier was mainly the condom stigma, namely regarding using condom as symbols of distrust or HIV/sexually transmitted infections (STIs) prevention, or as violating traditional cognition of sex, or as an embarrassing topic; environmental/structural-level barriers included situational unavailability, unaffordability of condoms and power imbalance in the sexual relationship.

Conclusion

This meta-synthesis offered in-depth understanding of condom use barriers for MSM and could guide the development of multifactorial interventions according to the identified barriers, especially targeting to reduce condom stigma, which has not been focused and intervened previously.
Comparing access to sexual and reproductive health services among sexual minority youths and their peers: findings from a national survey in China
Authors: Liang Yun , Hee Jiayi , Peng Chunxiao , Li Chunyan , Cao Wenzhen , Tang Kun
Published: November 2022

Background

Little is known about the access to measures of sexual and reproductive health (SRH) services among sexual minority communities in China, where sexuality-related stigma and discrimination remains high. The aim of this study is to investigate access to measures of SRH services among Chinese sexual minority youths (SMY) aged 17 to 24 years old.

Methods

This cross-sectional study utilizes data on 54,580 youths from the 2019–2020 National College Student Survey on Sexual and Reproductive Health, conducted across 31 provinces in mainland China. Multivariable logistic regression modelling was utilized to assess the access to SRH services among Chinese youth with different self-reported sexual orientation.

Results

The majority of respondents identified as heterosexual (77.6%). The remaining respondents identified as bisexual (9.0%), lesbian or gay (2.8%), others (3.02%), or unknown (7.51%). Gay men reported greater access to free contraceptives at health centers (OR 1.62, 95% CI: 1.32–1.99) and were more likely to have receive medical treatment for sexual and reproductive issues (OR 1.83, 95% CI: 1.26–2.63) compared to heterosexual men. Gay and bisexual men were also more likely to use condom at first sexual intercourse compared to heterosexual men (gay men: OR 1.38, 95% CI: 1.13–1.68; bisexual men: OR 1.33, 95% CI: 1.03–1.71). However, the associations were reversed among women (lesbians: OR 0.05, 95% CI: 0.03 to 0.08; bisexuals: 0.75, 95% CI: 0.65 to 0.86).

Conclusions

Although SMY reported higher utilization of SRH services compared to their heterosexual counterparts, access to SRH services remains low among Chinese youths. Greater focus should be placed on improving access to SMY-friendly SRH services among Chinese youths.
Adult essential extracorporeal membrane oxygenation (ECMO) skills for use in an e-learning program for ICU physicians, nurses and perfusionists: a consensus by a modified Delphi questionnaire
Authors: Peperstraete Harlinde , Steenhout Annelien , De Somer Filip , Depuydt Pieter , Hoste Eric , Van Herzeele Isabelle
Published: November 2022

Background

Education in ECMO starts with basic theory and physiology. For this type of training, self-assessment e-learning modules may be beneficial. The aim of this study was to generate consensus on essential ECMO skills involving various professional groups involved in caring for ECMO patients. These skills can be used for educational purposes: development of an e-learning program and fine-tuning of ECMO-simulation programs.

Methods

Experts worldwide received an e-mail inviting them to participate in the modified Delphi questionnaire. A mixture of ECMO experts was contacted. The expert list was formed based on their scientific track record mainly in adult ECMO (research, publications, and invited presentations). This survey consisted of carefully designed questionnaires, organized into three categories, namely knowledge skills, technical skills, and attitudes. Each statement considered a skill and was rated on a 5-point Likert-scale and qualitative comments were made if needed. Based on the summarized information and feedback, the next round Delphi questionnaire was developed. A statement was considered as a key competency when at least 80% of the experts agreed or strongly agreed (rating 4/5 and 5/5) with the statement. Cronbach’s Alpha score tested internal consistency. Intraclass correlation coefficient was used as reliability index for interrater consistency and agreement.

Results

Consensus was achieved in two rounds. Response rate in the first round was 45.3% (48/106) and 60.4% (29/48) completed the second round. Experts had respectively for the first and second round: a mean age of 43.7 years (8.2) and 43.4 (8.8), a median level of experience of 11.0 years [7.0-15.0] and 12.0 years [8.3-14.8]. Consensus was achieved with 29 experts from Australia (2), Belgium (16), France (1), Germany (1), Italy (1), Russia (2), Spain (1), Sweden, (1), The Netherlands (4). The consensus achieved in the first round was 90.9% for the statements about knowledge, 54.5% about technical skills and 75.0% about attitudes. Consensus increased in the second round: 94.6% about knowledge skills, 90.9% about technical skills and 75.0% about attitudes.

Conclusion

An expert consensus was accomplished about the content of “adult essential ECMO skills”. This consensus was mainly created with participation of physicians, as the response rate for nurses and perfusion decreased in the second round.