bluuebunny/crossref_metadata_2025 huggingface dataset:
FBXW7β isoform drives transcriptional activation of the proinflammatory TNF cluster in human pro-B cells
Authors: Yang Scarlett Y. , Hayer Katharina E. , Fazelinia Hossein , Spruce Lynn A. , Asnani Mukta , Black Kathryn L. , Naqvi Ammar S. , Pillai Vinodh , Barash Yoseph , Elenitoba-Johnson Kojo S. J. , Thomas-Tikhonenko Andrei
Published: November 2022

Noncanonical exon usage plays many important roles in cellular phenotypes, but its contribution to human B-cell development remains sketchily understood. To fill this gap, we collected various B-cell fractions from bone marrow (BM) and tonsil donors, performed RNA sequencing, and examined transcript variants. We identified 150 genes that harbor local splicing variations in all pairwise comparisons. One of them encodes FBXW7, an E3 ubiquitin ligase implicated as a driver in several blood cancers. Surprisingly, we discovered that in normal human pro-B cells, the predominant transcript used an alternative first exon to produce the poorly characterized FBXW7β isoform, previously thought to be restricted to neural tissues. The FBXW7β transcript was also abundant in cell lines and primary samples of pediatric B-cell acute lymphoblastic leukemia (B-ALL), which originates in the BM. When overexpressed in a heterologous cell system, this transcript yielded the expected protein product, as judged by anti-FLAG immunoblotting and mass spectrometry. Furthermore, in REH B-ALL cells, FBXW7β mRNA was the only FBXW7 isoform enriched in the polyribosome fraction. To shed light on possible functions of FBXW7β, we used gain- and loss-of-function approaches and identified an FBXW7-dependent inflammatory gene signature, apparent in a subset of B-ALL with high FBXW7β expression. This signature contained several members of the tumor necrosis factor superfamily, including those comprising the HLA Class III cluster (LTB, LST1, NCR3, LTA, and NFKBIL1). Our findings suggest that FBXW7β expression drives proinflammatory responses, which could contribute to normal B-cell development, leukemogenesis, and responses to anticancer therapies.
MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis
Authors: Boitelle A , Gosset P , Copin MC , Vanhee D , Marquette CH , Wallaert B , Gosselin B , Tonnel AB
Published: November 2022

Exposure to coal dust leads to the development of coal worker's pneumoconiosis (CWP), a disease associated with an accumulation of macrophages in the lower respiratory tract. Mechanisms controlling monocyte recruitment are still poorly understood. Since monocyte chemoattractant protein-1 (MCP-1) is recognized as a potent chemotactic factor for blood monocytes, we analysed the presence of MCP-1 in the pulmonary compartment of patients with CWP. Bronchoalveolar lavage fluid (BALF) from 16 nonsmoking control subjects and 27 nonsmoking CWP patients (16 with simple pneumoconiosis (SP) and 11 with progressive massive fibrosis (PMF)) was analysed. Alveolar macrophages (AMs) were purified by adherence and BALF was concentrated tenfold by lyophilization. MCP-1 was measured in BALF and in 3 h AM supernatants using a sandwich enzyme-linked immunosorbent assay (ELISA). The localization of MCP-1 in lung tissue was determined by immunohistochemistry on tissue sections from three patients with CWP and two control subjects. MCP-1 levels were significantly higher in concentrated BALF from patients with SP or PMF (median 370 and 555 pg x mL-1, respectively) than in those from control subjects (median 11 pg x mL-1) (p<0.001). Released MCP-1 in AM supernatants was enhanced in patients with CWP (median 83 pg x mL-1) but compared to controls (median 41 pg x mL-1) this level did not reach significance. Although significantly increased, AM counts in BALF from patients with CWP did not correlate with MCP-1 levels. MCP-1 levels in BALF correlated with MCP-1 levels in AM supernatants (p=0.47; p<0.02). In control lung specimens, MCP-1 was expressed by a few AMs, type II pneumocytes and perivascular smooth muscle cells. CWP sections were characterized by an increased number of AMs and mainly by the presence of fibroblasts (in the myogenic area of fibrotic lesions) and hyperplastic type II pneumocytes, which were strongly immunostained for MCP-1. Our data demonstrate that: 1) patients with coal worker's pneumoconiosis have a marked pulmonary overproduction of monocyte chemoattractant protein-1; and 2) in addition to alveolar macrophages, fibroblasts (probably myofibroblasts) and hyperplastic type II pneumocytes may also be responsible for this increased level of monocyte chemoattractant protein-1 in coal worker's pneumoconiosis.
Comparison of nitrogen mustard, cytarabine and dacarbazine as pleural sclerosing agents in rabbits
Authors: Marchi E , Vargas FS , Teixeira LR , Fagundes DJ , Silva LM , Carmo AO , Light RW
Published: November 2022

We have previously shown that the intrapleural injection of mitozantrone but not bleomycin resulted in pleural fibrosis. Mechlorethamine hydrochloride (nitrogen mustard) was used extensively in the past to control malignant effusions, with relatively good success. The objective of this study was to determine if the intrapleural injection of nitrogen mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen mustard as well as those of cytarabine and dacarbazine. Nitrogen mustard (0.4 and 0.8 mg x kg(-1)), cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were instilled intrapleurally into anaesthetized rabbits. Twenty eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.8 mg x kg(-1) nitrogen mustard was effective in creating pleural fibrosis, either grossly or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg x kg(-1) nitrogen mustard was 3.2+/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0.8. The intrapleural injection of 0.4 mg x kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were ineffective in producing pleurodesis. From this study, we conclude that the intrapleural injection of 0.8 mg x kg(-1) of nitrogen mustard produces clinically significant pleurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg x kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.
Radiology of pulmonary turberculosis and human immunodeficiency virus infection in Gulu, Uganda
Authors: Awil PO , Bowlin SJ , Daniel TM
Published: November 2022

Pulmonary tuberculosis is a major complication of human immunodeficiency virus (HIV) infection. The radiographic manifestations of pulmonary tuberculosis in HIV-infected patients are not typical of those seen in immunologically normal individuals. We sought to determine whether these manifestations provide clues to the pathogenesis of tuberculosis in HIV-infected persons. The radiographic manifestations of pulmonary tuberculosis were reviewed and classified in 82 HIV-positive and 53 HIV-negative tuberculous patients in Gulu, Uganda. Pulmonary presentations of tuberculosis were more acute in HIV-positive patients, and often included hilar or mediastinal adenopathy and pleural effusions, findings typical of primary tuberculosis in immunologically normal individuals. Many patients also had chronic forms of tuberculosis, either alone or in combination with acute disease. The findings of this study support the hypothesis that reactivation of latent infections and progression of pre-existent chronic disease produce a substantial portion of the tuberculosis burden of HIV-positive persons in Uganda. Tuberculosis control efforts should extend beyond efforts at decreasing transmission of new infections.
Bronchial gamma delta T-lymphocytes and expression of heat shock proteins in mild asthma
Authors: Fajac I , Roisman GL , Lacronique J , Polla BS , Dusser DJ
Published: November 2022

Heat shock proteins (HSPs), which are important targets for gammadelta T-lymphocytes, are thought to play a role in inflammatory and immune diseases. The purpose of this study was to characterize, in asthma, the presence and distribution of alphabeta and gammadelta T-lymphocytes and of hsp60, hsp70 and hsp90 in bronchial biopsies, and to seek for a co-localization of gammadelta T-cells and HSPs. Ten subjects with mild atopic asthma and nine control subjects underwent fibreoptic bronchoscopy and bronchial biopsies, to which specific monoclonal antibodies and immunohistochemical techniques were applied. T-lymphocytes present in bronchi both of asthmatic and control subjects were predominantly of the alphabeta T-cell receptor phenotype (median 642 cells x mm(-2) (range 85-1,510 cells x mm(-2)), and 855 cells x mm(-2) (286-2,424 cells x mm(-2)), respectively), whereas, gammadelta T-lymphocytes were always rare (median 26 cells x mm(-2) (range 0-114 cells x mm(-2)), and 0 cells x mm(-2 (0-57 cells x mm(-2), respectively). Both in asthmatic and control subjects, bronchial epithelium was positive for hsp60, hsp70 and hsp90. There was no significant difference in the percentages of positive epithelial cells between asthmatic and control subjects. No co-localization of HSPs and gammadelta T-cells was observed. Our findings do not support the hypothesis that heat shock proteins and gammadelta T-cells play an important role in inflammatory and immune responses in mild asthma.
Compliance with inhaled medication and self-treatment guidelines following a self-management programme in adult asthmatics
Authors: van der Palen J , Klein JJ , Rovers MM
Published: November 2022

Two of the principal components of self-management are compliance with medication and adherence to self-treatment guidelines. The aim of this study was to evaluate compliance objectively. Twenty two adult asthmatics attended a self-management programme. During a 2 week run-in period, compliance with inhaled steroids and peak expiratory flow (PEF) were electronically-registered. For PEF this resulted in a personal best value (PBV). Subsequently, patients attended four educational group sessions. During the four weeks of follow-up, patients were instructed to measure their PEF on a fixed day of the week and when they experienced an increase in symptoms. If PEF fell below 80% of PBV, patients had to double their use of inhaled steroids; if PEF fell below 60%, they had to start a short course of oral steroids. During run-in, mean compliance was 83% and compliance per patient varied from 6 to 106%. During follow-up, on days without exacerbation, compliance with inhaled steroids increased by 12% (95% confidence interval (95% CI) 3-21%) compared to run-in, ranging 21-200%. On days when patients should have doubled their inhaled steroids, compliance decreased by 28% (95% CI -39 to -17), and compliance ranged 46-94%. Of the 10 patients who should have doubled their medication, only three did so, whilst four increased the use of inhaled steroids but only by one or two puffs; three patients did not alter their behaviour. In five patients (24%) PEF fell below 60% of their PBV, after which four started prednisolone (self-report). In conclusion, even after a formal self-management programme, patients with asthma comply only partially to self-treatment guidelines. Most are willing to increase, but not double, their inhaled steroids. This suggests that more emphasis is needed to reassure patients about the safety of inhaled steroids.
Estimation of random errors in respiratory resistance and reactance measured by the forced oscillation technique
Authors: Farre R , Rotger M , Navajas D
Published: November 2022

The forced oscillation technique (FOT) allows the measurement of respiratory resistance (Rrs) and reactance (Xrs) and their associated coherence (gamma2). To avoid unreliable data, it is usual to reject Rrs and Xrs measurements with a gamma2 <0.95. This procedure makes it difficult to obtain acceptable data at the lowest frequencies of interest. The aim of this study was to derive expressions to compute the random error of Rrs and Xrs from gamma2 and the number (N) of data blocks involved in a FOT measurement. To this end, we developed theoretical equations for the variances and covariances of the pressure and flow auto- and cross-spectra used to compute Rrs and Xrs. Random errors of Rrs and Xrs were found to depend on the values of Rrs and Xrs, and to be proportional to ((1-gamma2)/(2 x N x gamma2))1/2. Reliable Rrs and Xrs data can be obtained in measurements with low gamma2 by enlarging the data recording (i.e. N). Therefore, the error equations derived may be useful to extend the frequency band of the forced oscillation technique to frequencies lower than usual, characterized by low coherence.
Method to produce American Thoracic Society flow-time waveforms using a mechanical pump
Authors: Hankinson JL , Reynolds JS , Das MK , Viola JO
Published: November 2022

The American Thoracic Society (ATS) recently adopted a new set of 26 standard flow-time waveforms for use in testing both diagnostic and monitoring devices. Some of these waveforms have a higher frequency content than present in the ATS-24 standard volume-time waveforms, which, when produced by a mechanical pump, may result in a pump flow output that is less than the desired flow due to gas compression losses within the pump. To investigate the effects of gas compression, a mechanical pump was used to generate the necessary flows to test mini-Wright and Assess peak expiratory flow (PEF) meters. Flow output from the pump was measured by two different independent methods, a pneumotachometer and a method based on piston displacement and pressure measured within the pump. Measuring output flow based on piston displacement and pressure has been validated using a pneumotachometer and mini-Wright PEF meter, and found to accurately measure pump output. This method introduces less resistance (lower back-pressure) and dead space volume than using a pneumotachometer in series with the meter under test. Pump output flow was found to be lower than the desired flow both with the mini-Wright and Assess meters (for waveform No. 26, PEFs 7.1 and 10.9% lower, respectively). To compensate for losses due to gas compression, we have developed a method of deriving new input waveforms, which, when used to drive a commercially available mechanical pump, accurately and reliably produces the 26 ATS flow-time waveforms, even those with the fastest rise-times.
Cardiovascular consequences of fibreoptic bronchoscopy
Authors: Davies L , Mister R , Spence DP , Calverley PM , Earis JE , Pearson MG
Published: November 2022

Fibreoptic bronchoscopy (FOB) is now commonly performed, and the number of elderly patients undergoing the procedure is increasing. Problems with oxygenation during FOB are well-recognised, but there are few data about its cardiovascular effects. Forty five patients (median age 65 yrs) undergoing elective FOB were studied prospectively. Patients were connected to a 12-lead computerized electrocardiographic recorder, a finger plethysmographic blood pressure (FPBP) monitor and pulse oximeter. Forty three patients were sedated with fentanyl and droperidol, and all were given 5 mL 2.5% cocaine intratracheally and xylocaine spray to the pharynx. Mean sphygmomanometric cuff blood pressure was raised initially (167/88 mmHg). Mean blood pressure recorded by FPBP rose on intratracheal injection (178/96 mmHg) and remained high throughout the procedure. Mean (SD) initial cardiac frequency was 93 (5.1) beats x min(-1) and rose to 134 (7.5) beats x min(-1) during the procedure. Four of the 45 patients showed unexpected ST segment depression of >1 mm for >1 min, and a further three developed bundle branch block. These seven patients had significantly greater tachycardia (152 vs 131 beats x min(-1)) and higher blood pressure (238/131 vs 207/109 mmHg). They were older (72 vs 61 yrs), had smoked more (63 vs 39 pack-years), but had similar lung function and similar changes in oxygen saturation. Oxygen desaturation occurred in 19 patients and this was associated with poor lung function (69 vs 84% predicted forced expiratory volume in one second), but was independent of the cardiovascular changes. Significant cardiovascular changes occur during fibreoptic bronchoscopy, with evidence of cardiac strain in 21% of patients over the age of 60 yrs.
Nitric oxide, the biological mediator of the decade: fact or fiction?
Authors: Singh S , Evans TW
Published: November 2022

Nitric oxide (NO), an atmospheric gas and free radical, is also an important biological mediator in animals and humans. Its enzymatic synthesis by constitutive (c) and inducible (i) isoforms of NO synthase (NOS) and its reactions with other biological molecules such as reactive oxygen species are well characterized. NO modulates pulmonary and systemic vascular tone through its vasodilator property. It has antithrombotic functions and mediates some consequences of the innate and acute inflammatory responses; cytokines and bacterial toxins induce widespread expression of iNOS associated with microvascular and haemodynamic changes in sepsis. Within the lungs, a diminution of NO production is implicated in pathological states associated with pulmonary hypertension, such as acute respiratory distress syndrome: inhaled NO is a selective pulmonary vasodilator and can improve ventilation-perfusion mismatch. However, it may have deleterious effects through modulating hypoxic pulmonary vasoconstriction. Inhibitors of NOS may be of benefit in inotrope-refractory septic shock, but toxicity of newly developed selective iNOS inhibitors have prevented clinical trials of efficacy. An expanding literature on the origins and measurement of NO in exhaled breath implicates NO as a potentially useful marker of disease activity in respiratory tract inflammation in the future. This report reviews some aspects of research into the clinical importance of nitric oxide.
Sicca syndrome and silicoproteinosis in a dental technician
Authors: Orriols R , Ferrer J , Tura JM , Xaus C , Coloma R
Published: November 2022

Secondary sicca syndrome has been described in silicotic and exposed nonpneumoconiotic individuals. Systemic autoimmune pathogenic mechanisms have been thought to be responsible. Salivary gland mineral deposition has not so far been implicated. We describe the case of a dental technician who sand-blasted dental prostheses and developed silicoproteinosis and sicca syndrome. Immunological studies were negative. Scanning electron microscopy study and energy-dispersive X-ray analysis were carried out in the patient's lung and salivary gland and in two salivary glands from nonexposed individuals diagnosed with sicca syndrome. High peaks of silicon and aluminium were detected in the patient's lung and salivary gland. Silicon/sulphur and aluminium/sulphur ratios were higher in the patient's glands (0.612 and 0.402, respectively) than in the two control salivary glands (0.193 and 0 and 0.127 and 0, respectively). We suggest that, in this case, sicca syndrome could have been caused by inorganic deposition.
Lung and blood T-cell receptor repertoire in extrinsic allergic alveolitis
Authors: Wahlstrom J , Berlin M , Lundgren R , Olerup O , Wigzell H , Eklund A , Grunewald J
Published: November 2022

Patients with extrinsic allergic alveolitis (EAA) have accumulations of T-lymphocytes in their lungs. CD8+ lung T-cells, in particular, have been implicated in the pathogenesis of EAA. The objective of the present study was to analyse the T-cell receptor (TCR) V alpha and V beta gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBLs) before and after treatment. Twelve patients with clinical signs of extrinsic allergic alveolitis were studied at disease onset, and nine of the 12 were also studied after treatment and clinical recovery. Lung cells, obtained by bronchoalveolar lavage (BAL), and paired PBL samples were analysed by flow cytometry using a panel of anti-TCR V monoclonal antibodies. The changes in TCR V gene usage were most pronounced in BAL CD8+ cells, as compared to the BAL CD4+, PBL CD8+ and PBL CD4+ subsets. At disease onset, 10 of the 12 patients had lung restricted expansions of CD8+ T-cells using a particular V alpha or V beta gene segment, and 8 of the 12 patients had CD8+ T-cell expansions in PBL. For the patients in whom a follow-up was possible, a majority of the expansions in the lungs were normalized, whereas most of the expansions in PBL remained. An over-representation of human leucocyte antigen (HLA)-DR2 (15) was detected, particularly among patients with farmer's lung. An increased selected T-cell receptor V gene usage may follow specific interactions between T-cells and antigens. In extrinsic allergic alveolitis, we determined that such expansions occur most frequently in the lung CD8+ T-cells. Since most expansions of lung CD8+ T-cells normalized with clinical improvement, these are further implicated in the pathogenesis of extrinsic allergic alveolitis.
Altered accessory cell function of alveolar macrophages: a possible mechanism for induction of Th2 secretory profile in idiopathic pulmonary fibrosis
Authors: Furuie H , Yamasaki H , Suga M , Ando M
Published: November 2022

Alveolar macrophages (AMs) are considered to play a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent studies have revealed a predominance of the type-2 T-helper (Th2) cytokine pattern of inflammatory response in the pulmonary interstitium in IPF. The aim of the present study was to determine whether or not the altered accessory cell function of AMs could account for the Th2 pattern of chronic inflammation in IPF. The levels of various cytokines were measured in the supernatants of soluble anti-CD3 monoclonal antibody (MoAb)-stimulated T-cells, co-cultured with autologous AMs, by enzyme-linked immunosorbent assay (ELISA). Cells from six patients with IPF and from nine normal volunteers (five nonsmokers and four smokers) were examined. The inhibitory effect of interleukin (IL)-10 on the accessory cell function of AMs and the expression of CD80 and CD86 on AMs were also investigated. IL-4 and IL-5 levels were significantly higher in the co-cultures from patients with IPF than in those from normal volunteers. IL-2, interferon-gamma (IFN-gamma), and IL-10 production in these co-cultures did not differ. IL-10 suppressed T-cell proliferation in co-cultures with AMs from healthy volunteers (smokers and nonsmokers), but not with AMs from patients with IPF. Expression of CD80 and CD86 on AMs from these groups did not differ. Thus, the altered accessory cell function of alveolar macrophages from patients with idiopathic pulmonary fibrosis may possibly relate to the pattern of type-2 T-helper cytokine production in response to inflammation.
Effects of two weeks of topical budesonide treatment on microvascular exudative responsiveness in healthy human nasal airways
Authors: Greiff L , Andersson M , Svensson C , Akerlund A , Alkner U , Persson CG
Published: November 2022

Extravasation and luminal entry of plasma (mucosal exudation) is not only a key feature of airway inflammation in rhinitis and asthma but also a major first-line respiratory defence mechanism. Topical steroids are effective antiexudative agents in disease but, so far, little is known about the direct effects of these drugs on the responsiveness of the microcirculation in human airways. In this study, the effects of prolonged budesonide treatment on histamine-induced mucosal exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were carried out before and late in the treatment periods. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. Histamine produced concentration-dependent mucosal exudation of plasma before as well as after treatment with either placebo or budesonide. The topical steroid treatment only marginally (1.8 fold) decreased the response to the low concentration histamine (40 microg x mL(-1)) and, although it was significantly (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant mucosal exudation of plasma in the budesonide group. If the present observations are extrapolated to inflammatory conditions, the antiexudative effects of topical steroids in rhinitis (and asthma) may reflect only a small degree of microvascular antipermeability effects. We suggest that topical steroid treatment may not impede mucosal exudation responses when called for in acute human airway defence reactions.
Short-term effects of particulate air pollution on respiratory morbidity in asthmatic children
Authors: Peters A , Dockery DW , Heinrich J , Wichmann HE
Published: November 2022

Short-term effects of air pollution (consisting primarily of sulphur dioxide and particulate matter but with low acidity) on respiratory morbidity were studied in asthmatic children from Sokolov, Czech Republic. Eighty nine children with asthma, who recorded daily peak expiratory flow measurements, symptoms and medication use in a diary, were analysed for 7 months during the winter of 1991-1992. Air pollution measurements included: SO2, total suspended particulates (TSPs), inhalable particles, ie. particulate matter of aerodynamic diameter < or = 10 microm, particle strong acidity (PSA) and fine particle sulphate concentration (SO4). Linear and logistic regression analyses estimated the impact of air pollutants adjusted for trend, temperature and weekend and autocorrelated errors. Exposure to elevated levels of air pollution was associated with decreased peak expiratory flow rates, increased respiratory symptoms, increased prevalence of school absence and fever, and increased medication use. Prolonged exposure to particle SO4 showed the largest effect estimates. At the end of January, an air pollution episode occurred, during which respiratory symptoms, prevalence of fever, school absence and asthma medication increased. The association between respiratory symptoms and particulate SO4 was highly dependent on this episode, whilst the associations between lung function and SO4 as well as between fever and SO4 were still observed when this air pollution episode was excluded. Some evidence was found that exposure to air pollution might have enhanced the respiratory symptoms while children were experiencing respiratory infections. In this study, a panel of children with mild asthma experienced small decreases in peak expiratory flow and increased dyspnoea in association with fine particles formed during air pollution episodes.
Respiratory resistance by the forced oscillation technique in asthmatic children and cystic fibrosis patients
Authors: Lebecque P , Stanescu D
Published: November 2022

Measurement of the total resistance of the respiratory system (Rrs) is an attractive alternative to measurement of forced expiratory volume in one second (FEV1) in young children because it requires minimal co-operation. The purpose of this study was to assess the ability of the forced oscillation technique (FOT) to detect airway obstruction in asthmatic children and in patients with cystic fibrosis (CF). Spirometry and Rrs were recorded in 45 asthmatic children (32 males and 13 females) and in 45 patients with CF (28 males and 17 females). Rrs was measured at 10 Hz with the Siregnost FD5 (Siemens, Germany). The asthmatic children were slightly younger than the patients with CF (10+/-3 vs 14+/-7 yrs), and had milder airway obstruction (FEV1 80+/-19 vs 66+/-27% of predicted). Rrs was significantly higher in the asthmatic children (6.6+/-1.7 cmH2O x L(-1) x s) than in the patients with CF (4.8+/-1.4 cmH2O x L(-1) x s). A normal FEV1 (> or = mean -2SD) was associated with a normal Rrs (< or = mean +2SD) in 17 of the 45 asthmatic children and in 13 of the 45 CF patients. By contrast, a low FEV1 (< mean -2SD) was associated with an increased Rrs (> mean +2SD) in 21 of the 45 asthmatic children, but in only 3 of the 45 CF patients. Thus, FEV1 and Rrs yielded concordant information in asthmatic children much more often (38 out of 45) than in CF patients (16 out of 45) (p < 0.001). In CF, Rrs failed to detect even severe airways obstruction. These findings might be accounted for by the inability of Rrs to reflect peripheral obstruction. We conclude that total respiratory resistance is suitable to assess airways obstruction in asthmatic children but not in cystic fibrosis patients.
Gas compression artefacts when testing peak expiratory flow meters with mechanically-driven syringes
Authors: Navajas D , Roca J , Farre R , Rotger M
Published: November 2022

Mechanically-driven syringes used to test peak expiratory flow (PEF) meters must produce the American Thoracic Society (ATS) standard waveforms with PEF accuracy of 2%. However, gas compression within the syringe could result in significant PEF inaccuracy when testing high resistance meters. The gas compression artefact was investigated in a mechanical syringe (PWG; MH Custom Design & Mfg L.C., Midvale, Ut, USA) of 13.6 L connected to a standard range mini-Wright PEF meter (Clement Clarke International, Harlow, UK). Scaled versions of the ATS standard waveform No. 24, with peak flows of 750 and 450 L x min(-1), were discharged through the PEF meter from different starting piston positions to vary syringe volume (Vsyr). The PEF recorded by the meter decreased linearly with increasing Vsyr. PEF decreased by 0.31 and 0.27% per litre for the ATS standard waveforms with PEF of 750 and 450 L x min(-1), respectively. The target PEF computed from piston displacement overread the actual PEF delivered into the PEF meter by approximately 4% when Vsyr = 13.6 L. Overreading fell to approximately 1% when Vsyr was reduced to 3.62 L. Therefore, gas compression error in commercially available large mechanical syringes can exceed the 2% inaccuracy limit when testing high resistance portable PEF meters. Measurements can be corrected for gas compression by linearly extrapolating PEF recordings to zero volume.
Pleural tuberculosis
Authors: Ferrer J
Published: November 2022

Tuberculous pleural effusions occur in up to 30% of patients with tuberculosis. It appears that the percentage of patients with pleural effusion is comparable in human immunodeficiency virus (HIV)-positive and HIV-negative individuals, although there is some evidence that HIV-positive patients with CD4+ counts <200 cells x mL(-1) are less likely to have a tuberculous pleural effusion. There has recently been a considerable amount of research dealing with the immunology of tuberculous pleurisy. At present, we have more evidence that activated cells produce cytokines in a complex pleural response to mycobacteria. Intramacrophage elimination of mycobacterial antigens, granuloma formation, direct neutralization of mycobacteria and fibrosis are the main facets of this reaction. With respect to diagnosis, adenosine deaminase and interferon gamma in pleural fluid have proved to be useful tests. Detection of mycobacterial deoxyribonucleic acid (DNA) by the polymerase chain reaction is an interesting test, but its usefulness in the diagnosis of tuberculous pleurisy needs further confirmation. The recommended treatment for tuberculous pleurisy is a 6 month regimen of isoniazid and rifampicin, with the addition of pyrazinamide in the first 2 months. HIV patients may require a longer treatment. The general use of corticosteroids is not recommended at this time, but they can be used in individuals who are markedly symptomatic.
Methods of examining induced sputum: do differences matter?
Authors: Kips JC , Peleman RA , Pauwels RA
Published: November 2022

Analysis of induced sputum has been proposed as a direct, relatively noninvasive method for the evaluation of airway inflammation in diseases such as asthma or chronic obstructive pulmonary disease (COPD). An important question in the validation of this technique concerns the potential influence of differences in the methods of examining sputum. Up to the present time, two basic techniques for processing sputum have been described. The first approach consists of selecting all viscid portions from the expectorated sample, whereas the second approach processes the whole expectorate, containing sputum plus saliva. Both processing techniques have been shown to provide valid and reliable data on the composition of the cellular and soluble fraction of induced sputum. From the data currently available, it would therefore appear that the usefulness of induced sputum as a method for assessing airway inflammation is not influenced by differences in the methods currently used for examining sputum.
Serum eosinophil cationic protein measurements in the management of perennial and periodic asthma: a prospective study
Authors: de Blay F , Purohit A , Stenger R , Gries P , Hamberger C , David B , Frossard N , Pauli G
Published: November 2022

We performed a prospective study in order: 1) to determine whether a correlation could be found between serum eosinophil cationic protein (ECP) levels and clinical and functional status in perennial asthmatics during a 5 month prospective study; and 2) to evaluate the relationship between allergic exposure and ECP levels in periodic asthmatics. Two groups of asthmatic patients were selected: a group of acutely ill perennial asthmatics and a group of periodic asthmatics. The acutely ill perennial asthmatics (n=22, mean age=39.4 yrs) were included on the basis of hospitalization for acute asthma. At the end of the hospitalization, there was a 5 month follow-up of clinical, functional and medication scores, as well as eosinophil counts and ECP levels. The periodic asthmatic group was composed of asthmatics sensitized to birch and tree pollens (n=10, mean age=33.8 yrs). The same measurement were performed on this group, before, during and after the pollen season. Under corticosteroid treatment in the acutely ill patients, there was a significant decrease in serum ECP levels between the first day of hospitalization and the day of discharge (mean: 23.2 microg x L(-1) and 9.5 microg x L(-1), respectively; p=0.006). No correlation was found between the clinical status, functional status and serum ECP levels during the 5 month follow-up. A significant increase in ECP levels was found in periodic asthmatics during the pollen season. Our results suggest that serum eosinophil cationic protein is a useful marker of allergen exposure and of acute asthma treatment. This could be of importance in the prevention and follow-up of allergic asthma; the value of serum eosinophil cationic protein measurements in the day-to-day management of adult asthmatics needs to be further clarified.
An undetected burden of asthma in Italy: the relationship between clinical and epidemiological diagnosis of asthma
Authors: de Marco R , Cerveri I , Bugiani M , Ferrari M , Verlato G
Published: November 2022

This study aimed to compare questions and tests used in asthma epidemiology with clinical diagnosis of current asthma and to assess the extent of undiagnosed asthma in Italy. Thus, 811 attenders to the second stage of the European Community Respiratory Health Survey were classified by panels of respiratory physicians as current asthmatics or not. Among those with a clinical diagnosis of asthma (n=105), 69% reported current wheezing and 68% asthma in their lifetime (ever asthma), while asthma attacks in the previous year and/or current treatment for asthma (self-reported current asthma) were mentioned by only 37%. Thirty two per cent did not mention asthma at any time, but nevertheless presented a rate of hospitalization close to that of people with self-reported current asthma. On the other hand, almost no subjects labelled nonasthmatics by clinicians (n=706) presented self-reported current asthma (99.7%), while some reported ever asthma (5%) or current wheezing (9%). A model simulation showed that, in its usual range (0-15%), asthma prevalence is markedly overestimated by the question on wheezing and underestimated by the questions on self-reported current asthma, with respect to clinical judgement. Prevalence estimates close to those obtained by clinical judgement were achieved by combining asthma-like symptoms in the previous year with the results of lung function and allergological tests, but especially by using the single question on ever asthma. In conclusion, the present results suggest that the question on ever asthma gives prevalence estimates close to those obtained by clinical judgement and that asthma is greatly underdiagnosed in Italy.
Bronchial reactivity to cigarette smoke in smokers: repeatability, relationship to methacholine reactivity, smoking and atopy
Authors: Jensen EJ , Dahl R , Steffensen F
Published: November 2022

Bronchial reactivity to cigarette smoke (CBR) in a cross-section of 98 smokers has been investigated. All participants were subjects to skin-prick tests to common allergens, lung function measurements and bronchial challenges with methacholine and cigarette smoke. In 38 participants a rechallenge with cigarettes was performed 1 h after the first cigarette challenge. Lung function indices analysed were: forced expiratory volume in one second (FEV1); maximal expiratory flow at 75% of the forced vital capacity (MEF75%); and forced mid-expiratory flow between 25 and 75% of the forced vital capacity (FEF(25-75%)). All participants were tested for asthma and allergy, and were required to provide information regarding respiratory symptoms, first degree relatives with asthma and allergy and smoking habits. A substantial decrease was seen in all lung function indices after 12 cigarette-smoke inhalations, but only FEV1 was related to other variables. The maximal mean percentage fall in FEV1 was 10%, which was directly related to the number of inhalations (p<0.05). In multiple regression analyses the percentage fall in FEV1 was directly related to: FEV1/vital capacity (VC) (p<0.01); to the asthmatic/bronchitic status (p<0.05); and to the accumulated and standardized cigarette consumption (p<0.05). The percentage fall in FEV1 bore no relationship to methacholine bronchial reactivity, sex or age and had a continuous distribution. The repeat challenge showed a smaller fall in FEV1 compared to the first challenge after 12 cigarette smoke inhalations (p<0.05). The percentage fall in FEV1 correlated after the first and the repeat challenge (p<0.05). Repeatability of the challenge could not be determined in this study because of tachyphylaxis. Bronchial reactivity to cigarette smoke is a tobacco smoke-specific bronchial response. All participants responded and the response showed a continuous distribution. Bronchial reactivity to cigarette smoke may be of importance for symptoms and prognosis in chronic bronchitis and chronic obstructive pulmonary disease and should be studied in relation to the degree of accelerated lung function loss in smokers and other cigarette induced lung abnormalities.
Nasal airflow resistance measurement: forced oscillation technique versus posterior rhinomanometry
Authors: Lorino AM , Lofaso F , Abi-Nader F , Drogou I , Dahan E , Zerah F , Harf A , Lorino H
Published: November 2022

This study was designed to determine whether nasal airflow resistance (Rn) which is nonlinear during tidal breathing, can be assessed by the forced oscillation (FO) technique. Rn values obtained by the FO technique and extrapolated to 0 Hz (Rn,FO) were compared to those assessed by posterior rhinomanometry at maximal tidal inspiratory flow (Rn,m), at a 0.5 L x s(-1) flow (Rn,F), and at a 1 hPa transnasal pressure (Rn,P). All Rn estimates were derived from the same inspiratory and expiratory nasal flow and transnasal pressure signals obtained during tidal nasal breathing whilst a forced flow was applied at the nose via a rigid nasal mask in 23 healthy volunteers, of whom 14 had additional measurements after vasoconstrictor treatment. In the basal state, no significant difference, and significant correlations (p<0.0001) were found between Rn,FO and the other Rn estimates. Only the regression line of Rn,FO versus Rn,m was not significantly different from the identity line. After nasal decongestion, Rn,P became significantly higher than the other Rn estimates (p<0.005). The regression line of Rn,FO versus Rn,m remained nonsignificantly different from the identity line. Similar results were observed regarding the percentage values of the different Rn estimates after decongestant treatment. This study shows that, despite its nonlinearity, Rn can be assessed by the FO technique, and that Rn,FO and Rn,m could be indifferently used as physiological indices of nasal patency. As the FO technique is more difficult to implement than the conventional rhinomanometry, its interest in rhinology appears not to be obvious.
Prognostic factors for mortality, intensive care unit and hospital admission due to SARS-CoV-2: a systematic review and meta-analysis of cohort studies in Europe
Authors: Vardavas Constantine I. , Mathioudakis Alexander G. , Nikitara Katerina , Stamatelopoulos Kimon , Georgiopoulos Georgios , Phalkey Revati , Leonardi-Bee Jo , Fernandez Esteve , Carnicer-Pont Dolors , Vestbo Jørgen , Semenza Jan C. , Deogan Charlotte , Suk Jonathan E. , Kramarz Piotr , Lamb Favelle , Penttinen Pasi
Published: November 2022

Background

As mortality from coronavirus disease 2019 (COVID-19) is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age-/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations.

Methods

We performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including death, hospitalisation, intensive care unit (ICU) admission and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11 June 2021 in Ovid Medline and Embase. Results are presented as odds ratios with 95% confidence intervals and absolute risk differences in deaths per 1000 COVID-19 patients.

Findings

We included 88 cohort studies with age-/gender-adjusted data from 6 653 207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke and liver disease.

Interpretation

The results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of nonpharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.
Recurrent headache and visual symptoms in a young man: a rare neuronal intranuclear inclusion disease case report
Authors: Su Ning , Mao He-Jiao , Mao Chen-Hui , Cui Li-Ying , Zhu Yi-Cheng , Zhou Yan , Ni Jun
Published: November 2022

Background

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease. Patients with NIID may present with heterogeneous clinical symptoms, including episodic encephalopathy, dementia, limb weakness, cerebellar ataxia, and autonomic dysfunction. Among the NIID cases reported in China, patients often have complicated and severe manifestations. Therefore, many clinicians do not consider the disease when the patient presents with relatively minor complaints.

Case presentation

We present the case of a 39-year-old man showing migraine-aura-like symptoms for the past 3 years. Brain magnetic resonance imaging (MRI) revealed hyperintense signals in the splenium of the corpus callosum and corticomedullary junction on diffusion-weighted imaging (DWI) over time. In addition, brain atrophy that was not concomitant with the patient’s age was detected while retrospectively reviewing the patient’s imaging results. Genetic analysis and skin biopsy confirmed a diagnosis of NIID. The patient was treated with sibelium, and the symptoms did not recur.

Discussion and Conclusions

Migraine-aura-like symptoms may be the predominant clinical presentation in young patients with NIID. Persistent high-intensity signals on DWI in the brain and early-onset brain atrophy might be clues for the diagnosis of NIID.
Secundiparas following a failed vacuum delivery—factors associated with a successful vaginal delivery: a historical prospective cohort
Authors: Reichman Orna , Ehrlich Zvi , Suday Ramy , Sela Hen , Gold Gila , Samueloff Arnon , Grisaru-Granovsky Sorina
Published: November 2022

Background

Few studies have focused on the delivery subsequent to a failed vacuum delivery (failed-VD) in secundiparas. The objective of the current study was to examine the factors associated with a vaginal delivery following a failed-VD.

Methods

An historical prospective cohort. Obstetric characteristics of secundiparas who underwent a planned caesarean delivery (CD) were compared to those who elected a trial of labour (TOLAC) at single medical-centre, throughout 2006–2019. The latter were further analysed to study for factures associated with successful vaginal birth (VBAC).

Results

Among the 115 secundiparas included, 89 (77%) underwent TOLAC. Compared to women who underwent an elective CD, those who underwent TOLAC were younger by a mean of 4 years, were more likely to have conceived spontaneously, and had a more advanced gestation by a mean of 10 days. VBAC was achieved in 62 women (70%). New-borns of women with VBAC had in average a lower birth weight compared to those with failed TOLAC, (-)195 g ± 396 g versus ( +)197 g ± 454 g respectively, P < 0.01. Having a higher neonatal birthweight at P2 by increments of 500 g, 400 g or 300 g was associated with a failed TOLAC; OR of 9.7 (95%CI; 2.3, 40.0), 11.5 (95%CI; 2.8, 46.7) and 4.5 (95%CI; 1.4, 13.9), respectively.

Conclusions

Among secundiparas with a previous CD due to a failed-VD, the absolute difference of neonatal BW was found to be significantly associated with achieving VBAC.