bluuebunny/crossref_metadata_2025 huggingface dataset:
Central sleep apnoea syndrome with upper airway collapse
Authors: Pepin JL , Pajon A , Veale D , Ferretti G , Levy P
Published: November 2022

We report on an 83 yr old man with hypersomnia and central sleep apnoea (CSA). He had several possible causes for CSA, including a central nervous system lesion, hypocapnia and anatomical narrowing of the airway at the hypopharyngeal level. We postulate that reduced central respiratory drive occurring in conjunction with upper airway narrowing may have led to central apnoeas. These in turn could have facilitated a complete passive hypopharyngeal collapse at the end of each apnoea, as visualized by somnofluoroscopy. The CSA could also have been favoured by respiratory instability due to chronic hypocapnia.
How do patients with either asthma or COPD perceive acute bronchodilation?
Authors: Noseda A , Schmerber J , Prigogine T , Yernault JC
Published: November 2022

The purpose of this study was to assess the perception of bronchodilation, as a change in shortness of breath on a bipolar visual analogue scale (VAS), in 16 asthmatics and 20 subjects with COPD. Bronchodilation was gradually induced by five consecutive terbutaline inhalations (cumulated dose 800 micrograms). The subjects were categorized into high and low perceivers, on the basis of a cut-off of 25% VAS line length (after the fifth inhalation). The quality of perception was studied on a within-subject basis by linear regression analysis of VAS ratings against changes in lung function, and was characterized in terms of strength of correlation (squared correlation coefficient, r2), slope, and VAS axis intercept. Fourteen out of 16 asthmatics, and 13 out of 20 COPD subjects, were high perceivers. In the COPD group, the high perceivers had a larger objective response--particularly in inspiratory vital capacity--than the low perceivers. The strongest correlation between subjective and objective response was obtained in asthmatics when the improvement in shortness of breath was evaluated against the decrease in specific inspiratory resistance (median r2 = 0.831). In COPD low perceivers, subjective and objective response were unrelated, while COPD high perceivers differed from the asthmatics by larger intercepts. The perceptual characteristics were unrelated to the degree of baseline obstruction, whilst a modest relationship (r = 0.51) was found between the increase in forced expiratory volume in one second (FEV1) and r2 of the VAS/delta FEV1 analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer risk in asthmatic subjects selected from hospital discharge registry
Authors: Kallen B , Gunnarskog J , Conradson TB
Published: November 2022

We wanted to study cancer risk in asthmatic subjects. With the use of central health registries, a cohort of 64,346 patients, treated in hospital with an asthma diagnosis, was followed with respect to cancer development. The observed numbers of different types of cancer were compared with the expected numbers, estimated from population data, with consideration taken to patient age, sex, survival, and the year of diagnosis. In general, a marked reduction of cancer incidence (2 out of 3 of the expected numbers) was found, with the exception of two cancer types: cancer of the respiratory tract and cancer of endocrine glands. A more noticeable reduction in cancer risk was seen for multiple myeloma, malignant melanoma, mammary cancer, uterine body cancer, and stomach cancer. The causes of this "protective effect" are not indicated by the present analysis, and need further study.
Weight loss in chronic obstructive pulmonary disease
Authors: Muers MF , Green JH
Published: November 2022

Weight loss occurs in about a third or more disabled patients with chronic obstructive pulmonary disease (COPD), and appears to be a poor prognostic factor. As such, it correlates only weakly with FEV1, transfer factor and other measures of respiratory physiology and is probably, to a certain extent, independent of them. Recent studies of basal metabolic rate (BMR) in COPD using steady-state, non-invasive calorimetry, have shown it to be elevated by 10-20% in up to 40% of such patients. It is likely that this represents true hypermetabolism per kilogram of fat free mass. An elevated BMR cannot be predicted from combinations of detailed lung function tests or arterial gases, as patients with similar physiology have differing BMRs. Thus, although an increased work of breathing is the probable explanation for some of the increase, other factors such as cytokines or possibly drug therapy almost certainly contribute. Muscle loss in weight-losing COPD appears to involve both type I and type II fibres, because of a combination of reduced calorie intake and disuse atrophy. Respiratory muscles share this fibre loss. Review of the controlled studies on nutritional supplementation in COPD suggests that an energy increase of about 30% is needed to achieve substantial weight gain and improve exercise tolerance. Fat-rich supplements have some theoretical advantages. Further work is needed particularly with regard to the determinants of the increased BMR in COPD, and the effect of longer term nutritional supplements on prognosis.
Differences in BAL fluid variables in interstitial lung diseases evaluated by discriminant analysis
Authors: Drent M , Mulder PG , Wagenaar SS , Hoogsteden HC , van Velzen-Blad H , van den Bosch JM
Published: November 2022

The aim of this study was to investigate the possibility of distinguishing between patients with similarities in clinical presentation, suffering from three frequently occurring interstitial lung diseases, by means of discriminant analysis, using a number of selected variables derived from bronchoalveolar lavage fluid (BALF) analysis. The study involved all 277 patients, who had an initial bronchoalveolar lavage (BAL) in the period 1980-1990. These patients belonged to the following diagnostic groups: sarcoidosis (n = 193), subacute extrinsic allergic alveolitis (EAA) (n = 39) and idiopathic pulmonary fibrosis (IPF) (n = 45). Thirty healthy volunteers were used as controls. Cellular and non-cellular constituents of BALF were evaluated. Variables, which could be used to discriminate among the three diagnostic groups were: yield of recovered BALF, total cell count, and percentages of alveolar macrophages, lymphocytes, polymorphonuclear neutrophils, eosinophils and plasma cells in BALF. When the set of data used to predict the membership of patients to diagnostic groups (test set) was the same as that in which the discriminant analysis was performed (learning set), 93% of the cases were correctly classified. This percentage decreased to 90%, however, when the test set was different from the learning set. It is possible to discriminate among patients with sarcoidosis, EAA or IPF with these selected variables. It appears that bronchoalveolar lavage (BAL) is useful as an adjunct in concert with other diagnostic methods.
Pulmonary toxicity of recombinant interleukin-2 plus lymphokine-activated killer cell therapy
Authors: Villani F , Galimberti M , Rizzi M , Manzi R
Published: November 2022

The aim of the present investigation was to evaluate lung toxicity in 15 patients affected by metastatic melanoma of different sites, and treated with recombinant interleukin-2 (rIL-2) plus lymphokine-activated killer (LAK) cells The treatment regimen included a first and a second course of rIL-2, separated by four consecutive daily leukaphereses. Autologous LAK cells were reinfused during the second course. Lung function was monitored before and after each rIL-2 administration. In the 12 patients who could be followed until completion of the therapy, spirometric parameters and transfer factor of the lungs for carbon monoxide (TLCO) decreased significantly during the first rIL-2 course, remained stable during leukapheresis, and declined significantly further during the second rIL-2 course. In the second phase, chest radiography documented some degree of pulmonary oedema, ranging from interstitial oedema to frank pulmonary oedema. A significant dose-dependent correlation was found between the cumulative rIL-2 dose and the decline in TLCO in the first course of therapy. Moreover, patients who developed symptomatic respiratory insufficiency (World Health Organisation grade III or IV) during the second course of therapy received a higher number of LAK cells than those who did not. The data support the hypothesis that LAK cells have an additional toxic effect on the lung.
Airways hyperresponsiveness, bronchodilator response, allergy and smoking predict improvement in FEV1 during long-term inhaled corticosteroid treatment. Dutch CNSLD Study Group
Authors: Kerstjens HA , Overbeek SE , Schouten JP , Brand PL , Postma DS
Published: November 2022

Although most patients with obstructive airways disease show some amelioration with long-term inhaled corticosteroid therapy, the extent of improvement may vary considerably between patients. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg.ml-1, and forced expiratory volume in one second (FEV1) < 95% confidence intervals (CI) of predicted normal. The independent influences of baseline PC20FEV1, inspiratory vital capacity (IVC), bronchodilator response, smoking habits, and allergy both on the "immediate" (within 3 months) response in FEV1 and the change in long-term (from 3 months onwards) slope of FEV1 with inhaled corticosteroids were analysed. Patients had a larger "immediate" improvement in their FEV1 with inhaled corticosteroids with each doubling doses lower PC20, with each ten-fold higher immunoglobulin E (IgE), and if they did not smoke. Total IgE proved a better independent predictor of "immediate" response than specific IgE for house dust mite, skin tests, or blood eosinophils. A more favourable long-term slope of FEV1 was predicted by a larger baseline bronchodilator response, but not by smoking. In conclusion, PC20, total IgE, and smoking habits are independent predictors of immediate treatment response to inhaled corticosteroids. Bronchodilator response is the single independent predictor of changes in long-term slope of FEV1 with corticosteroid treatment.
Virus-induced airway hyperresponsiveness in man
Authors: Sterk PJ
Published: November 2022

Airway hyperresponsiveness is the most prominent functional abnormality in asthma. Although its aetiology is still unclear, it is well-known that allergen exposure and virus infections can temporarily induce or aggravate airway hyperresponsiveness. Among these environmental factors, virus infections appear to be clinically most relevant, since recent epidemiological studies have shown that most asthma exacerbations in children are associated with positive nasopharyngeal viral identification. The pathogenesis of virus-induced airway hyperresponsiveness has been investigated by experimental virus infections in animals and in man. Intranasal inoculation and/or inhalation of live attenuated influenza virus, or certain strains of rhinovirus, have been shown to induce airway hyperresponsiveness to various bronchoconstrictor stimuli in man. This indicates that experimental virus-infection, like allergen challenge, is an appropriate investigational model of asthma. The mechanisms of virus-induced airway hyperresponsiveness are still unclear, but may, in part, be similar to those involved in the pathogenesis of asthma. Currently investigated hypothesis include: epithelial damage or dysfunction, immunological responses, inflammatory mediator release, cholinergic and/or noncholinergic reflexes, and impaired beta-adrenoceptor function. Careful experimental studies, using modern laboratory techniques, are needed to unravel the role of viruses in the development of airway hyperresponsiveness. The results of such studies can potentially lead to an improvement of future asthma management.
Allergic bronchopulmonary aspergillosis with middle lobe syndrome and allergic Aspergillus sinusitis
Authors: Shah A , Bhagat R , Panchal N , Jaggi OP , Khan ZU
Published: November 2022

A 55 year old male, who had a 12 yr history of rhinorrhoea and nasal blockage, presented with a middle lobe syndrome. Evaluation of the patient led to the diagnosis of concomitant allergic bronchopulmonary aspergillosis with allergic Aspergillus sinusitis, a rarely reported association.
Decline in FEV1 and airflow limitation related to occupational exposures in men of an urban community
Authors: Humerfelt S , Gulsvik A , Skjaerven R , Nilssen S , Kvale G , Sulheim O , Ramm E , Eilertsen E , Humerfelt SB
Published: November 2022

The purpose of this survey was to evaluate the effects of smoking and occupational exposures on the decline in forced expiratory volume in one second (FEV1), and the presence of airflow limitation (FEV1 x100/forced vital capacity (FVC) being < 65) at follow-up. A random sample of 1,933 men aged 22-54 years in Bergen, Norway, were invited into the survey. Smoking habits and measurements of FEV1 were recorded at the initial survey in 1965-1970 (n = 1,591) and at follow-up in 1988-1990 (n = 951). Past or present self-reported occupational exposures to eleven airborne agents (dusts, gases, vapours and fumes) and measurements of FVC were recorded at follow-up only. The decline in FEV1 was associated (p < 0.001) with age, body height and smoking. Smoking cessation reduced the decline to the level of lifetime nonsmokers. Accelerated decline in FEV1 was observed in subjects exposed to sulphur dioxide gas and to metal fumes. The adjusted decline in FEV1 increased progressively in subjects exposed to increasing numbers of occupational agents (test for trend: p < 0.01). Airflow limitation was observed in 9.5% at follow-up, and increased with age and cigarette consumption. In this community follow-up survey in men, smoking and occupational exposures to sulphur dioxide gas, metal fumes and the numbers of specific agents were found to be important predictors for accelerated decline in FEV1.
Air pollution levels, meteorological conditions and asthma symptoms
Authors: Forsberg B , Stjernberg N , Falk M , Lundback B , Wall S
Published: November 2022

We wanted to assess relations between the daily occurrence of asthma symptoms and fluctuations of air pollution concentrations and meteorological conditions. In a panel of 31 asthmatic patients residing in the town of Pitea in northern Sweden, severe symptoms of shortness of breath, wheeze, cough and phlegm were recorded in an asthma diary together with suspected causes. Sulphur dioxide, nitrogen dioxide, black smoke, relative humidity and temperature were used to evaluate the relationship to the environment. By using multivariate analyses, we found that daily variations in the particulate pollution levels, indicated by black smoke levels below the criteria limits, had significant effects on the risk of developing severe symptoms of shortness of breath. This association was stronger among 10 subjects, who had at least five incident days with severe shortness of breath. Meteorological conditions were not significant in the multivariate models. Cough and phlegm did not show significant relationships to any environmental condition that was evaluated. Only one-third of the subjects reported, at least once during the study, symptoms believed to be related to air pollutants, although we found significant correlations between the pollution levels and the frequency of pollution-related symptoms. We conclude that an association has been established for black smoke as pollutant and shortness of breath as respiratory symptom, and that in certain asthmatics, effects were occurring at lower particulate levels than suggested previously.
Assessment of airway inflammation in asthmatic patients by visual endoscopic scoring systems
Authors: Van Vyve T , Chanez P , Lacoste JY , Bousquet J , Michel FB , Godard P
Published: November 2022

Inflammation is a hallmark of bronchial asthma. Inflammatory cells both in bronchoalveolar lavage (BAL) and bronchial biopsies of asthmatic patients have been studied and correlated with functional or clinical parameters. We have recently attempted to assess airway inflammation by a visual endoscopic scoring system. The purpose of this study was to compare our own endoscopic scoring system with the bronchitis index previously described by Thompson and coworkers, and to determine whether these scores were correlated with clinical or functional parameters. Sixty asthmatics of variable severity (forced expiratory volume in one second (FEV1) 33-117% of predicted values) and 30 healthy volunteers were studied. The clinical severity of asthma was assessed by the clinical score as described by Aas in all of the patients, and in the last 15 patients by a daily symptom score. Beta 2-agonist consumption was recorded daily during a period of 7 days before the endoscopic procedure. During this period, circadian variation and day-to-day variation of peak expiratory flow rate (PEFR) were determined. During bronchoscopy, airway inflammation was assessed by two independent observers, prior to BAL, by visual inspection of each lobe and the lingula, and the results were quantitated using the bronchitis index and our endoscopic scoring system. Both endoscopic scores were significantly higher in asthmatics than in controls. A significant correlation was observed between the two endoscopic scores both in asthmatics and in controls. In asthmatics, a weak but significant correlation was found between both endoscopic scores and the daily symptom score, as well as the beta 2-agonist consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
Distearoyl phosphatidylglycerol liposomes improve surface and transport properties of CF mucus
Authors: Girod de Bentzmann S , Pierrot D , Fuchey C , Zahm JM , Morancais JL , Puchelle E
Published: November 2022

We have previously shown that a decreased level of phosphatidylglycerol in cystic fibrosis (CF) respiratory mucus is partly responsible for its marked adhesiveness and stickiness, which impair mucus transport, and that distearoyl phosphatidylglycerol (DSPG) was the most efficient form of phosphatidylglycerol in the enhancement of respiratory mucus clearance. The aim of our study was to analyse the effect of distearoyl phosphatidylglycerol liposomes on the transport by cough and cilia of cystic fibrosis respiratory mucus. The surface and transport properties of mucus were measured: 1) on native cystic fibrosis mucus; 2) on cystic fibrosis mucus complemented with DSPG liposomes at a non-cytotoxic concentration; and 3) on cystic fibrosis mucus complemented with water. The work of adhesion of cystic fibrosis mucus was significantly decreased by DSPG liposomes, but not by water. For mucociliary transport, the cystic fibrosis mucus was transported at a higher rate with DSPG liposomes and water compared to native cystic fibrosis mucus. The cough clearance of cystic fibrosis respiratory mucus was significantly improved in the presence of DSPG and water, but the effect was more pronounced with DSPG liposomes than with water. We conclude that the use of DSPG liposomes as a lubricating agent proves to be an interesting therapeutic approach for improving the cough and mucociliary transport in cystic fibrosis patients.
Short-term in vivo exposure to cigarette-smoke increases the fluorescence in rat alveolar macrophages
Authors: Skold CM , Andersson K , Hed J , Eklund A
Published: November 2022

Alveolar macrophages (AMs) from human smokers exhibit a strong intracellular fluorescence. In order to study the mechanisms behind the fluorescence, we wanted to determine whether it could be induced by short term exposure to smoke. We therefore exposed rats for either one or five days to cigarette smoke. AMs were recovered by bronchoalveolar lavage (BAL), and their fluorescence was quantified by flow cytofluorometry. AMs from rats exposed to two cigarettes, on a single occasion, showed an increased fluorescence compared to controls. The fluorescence was further enhanced by exposing rats to two cigarettes, for five consecutive days. Larger and more granular/complex AMs were more fluorescent than smaller and less granular/complex cells. Smoke-exposed rats (five consecutive days) lavaged immediately after the exposure, had less cells in their BAL fluid than control animals. However, when rats were lavaged three smoke-free days after the exposure, the cell recovery increased, probably due to less airway obstruction. In conclusion, we found that a short-term in vivo exposure to cigarette smoke results in an increased AM fluorescence. The findings can be one explanation for the strong fluorescence seen in AMs from human smokers, possibly due to endocytosis of fluorescent material.
Single-lung retransplantation for late graft failure
Authors: Fournier M , Sleiman C , Mal H , Groussard O , Mollo JL , Duchatelle JP , Andreassian B , Pariente R
Published: November 2022

In lung or heart-lung recipients, an irreversible graft-failure may develop in connection with chronic rejection, infection or bronchial complications. A limited number of transplant-recipients have undergone a retransplantation procedure in several centres. First results are discouraging, especially in the case of early retransplantation. We decided, 3 yrs ago, to evaluate the feasibility and benefits of single-lung retransplantation in lung-transplant recipients with late graft-failure. Eight consecutive single-lung retransplantations were performed in patients with previous single-lung (n = 7), or double-lung (n = 1) transplant. Primary graft and native lung were removed in 5 and 3 patients, respectively. The delay between the two surgical procedures was 16 +/- 10 months (range 6-37 months). Three patients died within 3 months. Long-term survivors experienced stable and satisfactory functional results (forced expiratory volume in one second (FEV1 63 +/- 21% predicted; range 40-103% predicted), with survival values ranging 8-20 months. One patient died of septic shock 16.5 months after retransplantation. The remaining four patients are alive. These data suggest that the retransplantation option could be considered in selected patients with late graft-failure. The final decision for retransplantation, however, is largely influenced by the current shortage of donor lungs.
No added benefit from nebulized amiloride in patients with cystic fibrosis
Authors: Graham A , Hasani A , Alton EW , Martin GP , Marriott C , Hodson ME , Clarke SW , Geddes DM
Published: November 2022

In cystic fibrosis (CF) airway epithelial sodium absorption is increased 2-3 fold. Since sodium absorption is inhibited by the sodium channel blocker amiloride, our aim was to assess its therapeutic benefit in cystic fibrosis. A randomized, double-blind, placebo-controlled, cross-over trial of nebulized amiloride was performed in 23 patients with cystic fibrosis. Amiloride or placebo was administered four times daily for two six month periods. Existing treatment was continued, and any infective exacerbations treated in the usual way. Fourteen patients completed the study. No significant changes occurred in forced expiratory volume in one second, forced vital capacity, oxygen saturation, body weight, sputum volume, culture and rheology, serum urea, and electrolytes, white cell count and erythrocyte sedimentation rate during either treatment period. The frequency of infective exacerbations was also not different in either treatment period. We were thus unable to confirm the benefit shown in the only other clinical trial of nebulized amiloride in cystic fibrosis and conclude that, in the presence of established treatment for cystic fibrosis lung disease, nebulized amiloride offers no additional clinical benefit.
Bronchoalveolar lavage in extrinsic allergic alveolitis: effect of time elapsed since antigen exposure
Authors: Drent M , van Velzen-Blad H , Diamant M , Wagenaar SS , Hoogsteden HC , van den Bosch JM
Published: November 2022

The aim of the present study was to investigate whether bronchoalveolar lavage (BAL) cell profile and immunoglobulin levels from patients with extrinsic allergic alveolitis (EAA) were related to the time elapsed between last antigen exposure and BAL. For this purpose, an analysis was performed of BAL fluid (BALF) obtained from 59 nonsmoking EAA patients at various time-points after termination of antigen exposure and BAL. BALF early after antigen provocation (group 1: < 24 h) contained high absolute and relative numbers of lymphocytes, neutrophils, eosinophils and mast cells, and a low relative number of alveolar macrophages. When obtained after recent antigen exposure (group 2: 2-7 days), BALF showed high numbers of lymphocytes, plasma cells and mast cells, and high levels of immunoglobulins M, G and A (IgM, IgG and IgA). In BAL obtained one week or more after the final antigen exposure, (Group 3: 8-30 days; Group 4: 1-12 months) the distribution of all constituents showed a tendency to return to normal values, with the exception of the lymphocytes. These results demonstrate that BAL cell profile and immunoglobulin levels in EAA are highly dependent on the time-point at which the material is obtained in relation to the last exposure to the causative antigen.
Phrenic nerve stimulation at the bedside in children; equipment and validation
Authors: Russell RI , Helps BA , Elliot MJ , Helms PJ
Published: November 2022

There is evidence that early diagnosis of postoperative phrenic nerve damage may improve outcome, by allowing early surgical treatment, in children following cardiac surgery. This has prompted the development of a simple method for measuring phrenic nerve latency at the bedside in children. We have evaluated the reproducibility of measurements made with this system in 11 children (4 months to 13 yrs) admitted for routine surgery or cardiac catheterizations, and have assessed the various components of variability inherent in the measurement of phrenic nerve latency. The overall variability of the phrenic nerve latency with this technique (95% confidence interval) is approximately +/- 1 ms, and differences greater than this between measurements are likely to reflect a real change in phrenic nerve function. Our results indicate that the bedside technique should be a useful method of the objective assessment of phrenic nerve function in children recovering from cardiac surgery.
Habitual snoring as a risk factor for acute vascular disease
Authors: Smirne S , Palazzi S , Zucconi M , Chierchia S , Ferini-Strambi L
Published: November 2022

We wanted to assess habitual snoring as a credible risk factor for acute vascular disease, mainly stroke and myocardial infarction. The patients selected for the study had been admitted to the hospital through the emergency department, and were evaluated by means of multidimensional interviews and clinical records: 164 had acute cerebrovascular disease, and 136 cardiovascular disease; 330 patients with nonvascular disease were the controls. The evaluation showed 48% of vascular disease patients to be habitual snorers, but only 30% of the controls; the difference was statistically significant. Compared with the controls, in the cerebrovascular patients the risk (odds ratio) associated with habitual snoring was significantly increased, and of the same order as the risk associated with age over 65 yrs, male gender, diabetes mellitus, and dyslipidaemia; whilst the risk associated with hypertension was higher. In the cardiovascular patients, the risk associated with habitual snoring was again significantly increased and of the same order as the risk associated with male gender, body mass index > 29 (kg.m-2), dyslipidaemia, heavy smoking, excessive alcohol intake and hypertension. A logistic regression analysis, entering the variables in the following order: age, gender, body mass index, diabetes, dyslipidaemia, smoking, alcohol, hypertension, and habitual snoring, showed that habitual snoring carries a significant risk factor for stroke and myocardial infarction, even after adjusting for other factors. Since habitual snoring carries a definite risk for acute vascular disease, we conclude that inquiring about it should become routine practice.
Congenital oesophageal respiratory tract fistula presenting in adult life
Authors: Danton MH , McMahon J , McGuigan J , Gibbons
Published: November 2022

Congenital oesophageal respiratory tract fistula presenting in adult life is rare. A tracheo-oesophageal and a broncho-oesophageal fistula presenting in a 22 year old female and 68 year male, respectively, are described. In both, symptoms of chronic recurrent pulmonary suppuration were initially attributed to alternative aetiologies, resulting in diagnostic delay and inappropriate management. Correct diagnosis was established by flexible bronchoscopy and oesophageal contrast studies. Surgical division of fistulae resulted in complete symptom resolution.
Bronchoalveolar lavage cell analysis in measles viral pneumonia
Authors: Myou S , Fujimura M , Yasui M , Ueno T , Matsuda T
Published: November 2022

Although the immunological changes due to measles virus infection, such as suppression of delayed skin reactivity and increase in soluble CD8 in peripheral blood, have been demonstrated, the immunological changes in the lung during measles viral pneumonia (MVP) have not been reported. The aim of this study was to clarify the intrapulmonary immunological changes in MVP. We analysed cell differentials and lymphocyte surface antigens of bronchoalveolar lavage (BAL) cells, both in the acute and the convalescent phase of MVP by flow-cytometry, using CD4+, CD8+, CD8+CD11b+ and CD8+CD11b- monoclonal antibodies in five patients and six healthy control subjects. The absolute numbers of CD8+ and CD8+CD11b- cells were significantly greater both in the acute and the convalescent phase compared with those in controls. The percentages of CD8+ and CD8+CD11b- cells in the acute phase were significantly greater than those in controls and the convalescent phase. The CD4/CD8 ratios in the acute phase were significantly smaller than those in the convalescent phase and controls. In conclusion, the intrapulmonary immunological changes with an increase in CD8+ and CD8+CD11b- cells in BAL fluid of MVP are thought to be the primary reaction in measles virus-infected lungs.
The 1992 Cournand Lecture. Asthma: past, present and future
Authors: Holgate ST
Published: November 2022

The association of asthma with the release of inflammatory mediators, through a mechanism that involves the immune system, has taken almost 100 years to evolve. While studies on lung tissue from patients who had died from asthma pointed to inflammation of the airways as a major lesion, clinicians have, until relatively recently, preferred to consider the disease more in terms of airways dysfunction rather than the cause(s) of this dysfunction. Bronchial mucosal biopsy and lavage has reaffirmed the view that asthma is a special type of airway inflammation involving mast cells and eosinophils which is orchestrated by T-lymphocytes of a Th2-like phenotype. Through cytokine release, these cells upregulate the function of mast cells and eosinophils. However, other factors are now considered important in the maintenance and chronicity of the inflammatory response both through tissue remodelling (e.g. fibrosis) and through the secretion of cytokines from epithelial, endothelial and constitutive mesenchymal cells. Evidence is accumulating that these events are genetically-linked although this is likely to involve multiple genes. Of special importance is the role of the environment both in the induction of allergen sensitised airways and the subsequent inflammatory response that follows. Included in these are intrauterine events, early life exposure to allergens, pollutants and viruses. If prevention of asthma is to be a future target for intervention, then future work should concentrate on those early genetic and environmental factors that initiate the inflammatory response rather than relying on strategies that attempt to reverse established disease.
Respiratory symptoms and their determinants in the general Spanish population: changes over 20 years
Authors: Miravitlles Marc , Soler-Cataluña Juan José , Soriano Joan B. , García-Río Francisco , de Lucas Pilar , Alfageme Inmaculada , Casanova Ciro , Rodríguez González-Moro José Miguel , Sánchez Guadalupe , Ancochea Julio , Cosío Borja G.
Published: November 2022

Background

Few large epidemiological studies have analysed the prevalence of respiratory symptoms and their determinants in the general adult population. We investigated the prevalence and determinants of respiratory symptoms and compared their prevalence with that of two previous studies conducted in 1999 and 2009.

Method

EPISCAN II was a multicentre, cross-sectional, population-based epidemiological study in individuals older than 40 years.

Results

A total of 9092 individuals were included. Up to 47.5% reported at least one respiratory symptom, being more frequent in women than in men (49.4%versus45.5%, p=0.0002) and with wheezing being the most frequent (33.7%) followed by dyspnoea (26.8%). The presence of any symptom was associated with female sex, higher body mass index (BMI), lower forced expiratory volume in 1 s (FEV1% pred), reduced physical activity, a higher Charlson index and the presence of anxiety and depression. Smoking was also significantly associated with having at least one respiratory symptom in a dose–response fashion (OR: 1.415, 1.916, 2.192 and 2.987 for 0–10, 10–20, 20–30 and >30 pack-years, respectively, all p<0.0001). The prevalence of symptoms remained quite similar over the last 20 years (wheezing 40%, 36% and 33.7% and dyspnoea 10.4%, 9.9% and 13.1% in 1999, 2009 and 2019, respectively).

Conclusions

Approximately half of the adult Spanish population have respiratory symptoms and this prevalence has remained quite stable over the last 20 years. Smoking remains the main factor associated with respiratory symptoms, but female sex, comorbidities, high BMI and low FEV1and low physical activity are also significantly associated with respiratory symptoms.
BICOSS: Bayesian iterative conditional stochastic search for GWAS
Authors: Williams Jacob , Ferreira Marco A. R. , Ji Tieming
Published: November 2022

Background

Single marker analysis (SMA) with linear mixed models for genome wide association studies has uncovered the contribution of genetic variants to many observed phenotypes. However, SMA has weak false discovery control. In addition, when a few variants have large effect sizes, SMA has low statistical power to detect small and medium effect sizes, leading to low recall of true causal single nucleotide polymorphisms (SNPs).

Results

We present the Bayesian Iterative Conditional Stochastic Search (BICOSS) method that controls false discovery rate and increases recall of variants with small and medium effect sizes. BICOSS iterates between a screening step and a Bayesian model selection step. A simulation study shows that, when compared to SMA, BICOSS dramatically reduces false discovery rate and allows for smaller effect sizes to be discovered. Finally, two real world applications show the utility and flexibility of BICOSS.

Conclusions

When compared to widely used SMA, BICOSS provides higher recall of true SNPs while dramatically reducing false discovery rate.
Identification of a novel miRNA-based recurrence and prognosis prediction biomarker for hepatocellular carcinoma
Authors: Zhang Xuanfeng , Zhang Dong , Bu Xuefeng , Zhang Xinhui , Cui Long
Published: November 2022

Background

A high recurrence rate has always been a serious problem for treatment of hepatocellular carcinoma (HCC). Exploring predictors of postoperative and posttransplantation recurrence in patients with HCC can guide treatment strategies for clinicians.

Results

In this study, logistic regression and multivariate Cox regression models were constructed with microRNA expression profile data from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO). The accuracy of predictions was assessed using receiver operating characteristic curve (ROC) and Kaplan‒Meier survival curve analyses. The results showed that the combination of 10 miRNAs (including hsa-miR-509-3p, hsa-miR-769-3p, hsa-miR-671-3p, hsa-miR-296-5p, hsa-miR-767-5p, hsa-miR-421, hsa-miR-193a-3p, hsa-miR-139-3p, hsa-miR-342-3p, and hsa-miR-193a-5p) accurately predicted postoperative and posttransplantation malignancy recurrence in HCC patients and was also valuable for prognostic evaluation of HCC patients. The 10-miRNA prediction model might assist doctors in making prognoses for HCC patients who have a high probability of relapse following surgery and in offering additional, individualized treatment to lessen that risk.
Genetic diversity and family groups detected in a coyote population with red wolf ancestry on Galveston Island, Texas
Authors: Barnes Tanner M. , Karlin Melissa , vonHoldt Bridgett M. , Adams Jennifer R. , Waits Lisette P. , Hinton Joseph W. , Henderson Josh , Brzeski Kristin E.
Published: November 2022

Background

Hybridization can be a conservation concern if genomic introgression leads to the loss of an endangered species’ unique genome, or when hybrid offspring are sterile or less fit than their parental species. Yet hybridization can also be an adaptive management tool if rare populations are inbred and have reduced genetic variation, and there is the opportunity to enhance genetic variation through hybridization. The red wolf (Canis rufus) is a critically endangered wolf endemic to the eastern United States, where all extant red wolves are descended from 14 founders which has led to elevated levels of inbreeding over time. Red wolves were considered extirpated from the wild by 1980, but before they disappeared, they interbred with encroaching coyotes creating a genetically admixed population of canids along coastal Texas and Louisiana. In 2018, a genetic study identified individuals on Galveston Island, Texas with significant amounts of red wolf ancestry. We collected 203 fecal samples from Galveston for a more in-depth analysis of this population to identify the amount of red wolf ancestry present and potential mechanisms that support retention of red wolf ancestry on the landscape.

Results

We identified 24 individual coyotes from Galveston Island and 8 from mainland Texas with greater than 10% red wolf ancestry. Two of those individuals from mainland Texas had greater than 50% red wolf ancestry estimates. Additionally, this population had 5 private alleles that were absent in the North American reference canid populations used in this study, which included 107 southeastern coyotes, 19 captive red wolves, and 38 gray wolves, possibly representing lost red wolf genetic variation. We also identified several individuals on Galveston Island and the mainland of Texas that retained a unique red wolf mitochondrial haplotype present in the red wolf founding population. On Galveston Island, we identified a minimum of four family groups and found coyotes on the island to be highly related, but not genetically depauperate. We did not find clear associations between red wolf ancestry estimates and landscape features, such as open green space or developed areas.

Conclusion

Our results confirm the presence of substantial red wolf ancestry persisting on Galveston Island and adjacent mainland Texas. This population has the potential to benefit future red wolf conservation efforts through novel reproductive techniques and possibly through de-introgression strategies, with the goals of recovering extinct red wolf genetic variation and reducing inbreeding within the species.
Evolution patterns of NBS genes in the genus Dendrobium and NBS-LRR gene expression in D. officinale by salicylic acid treatment
Authors: Yang Jiapeng , Xiong Caijun , Li Siyuan , Zhou Cheng , Li Lingli , Xue Qingyun , Liu Wei , Niu Zhitao , Ding Xiaoyu
Published: November 2022

Background

Dendrobium officinale Kimura et Migo, which contains rich polysaccharides, flavonoids and alkaloids, is a Traditional Chinese Medicine (TCM) with important economic benefits, while various pathogens have brought huge losses to its industrialization. NBS gene family is the largest class of plant disease resistance (R) genes, proteins of which are widely distributed in the upstream and downstream of the plant immune systems and are responsible for receiving infection signals and regulating gene expression respectively. It is of great significance for the subsequent disease resistance breeding of D. officinale to identify NBS genes by using the newly published high-quality chromosome-level D. officinale genome.

Results

In this study, a total of 655 NBS genes were uncovered from the genomes of D. officinale, D. nobile, D. chrysotoxum, V. planifolia, A. shenzhenica, P. equestris and A. thaliana. The phylogenetic results of CNL-type protein sequences showed that orchid NBS-LRR genes have significantly degenerated on branches a and b. The Dendrobium NBS gene homology analysis showed that the Dendrobium NBS genes have two obvious characteristics: type changing and NB-ARC domain degeneration. Because the NBS-LRR genes have both NB-ARC and LRR domains, 22 D. officinale NBS-LRR genes were used for subsequent analyses, such as gene structures, conserved motifs, cis-elements and functional annotation analyses. All these results suggested that D. officinale NBS-LRR genes take part in the ETI system, plant hormone signal transduction pathway and Ras signaling pathway. Finally, there were 1,677 DEGs identified from the salicylic acid (SA) treatment transcriptome data of D. officinale. Among them, six NBS-LRR genes (Dof013264, Dof020566, Dof019188, Dof019191, Dof020138 and Dof020707) were significantly up-regulated. However, only Dof020138 was closely related to other pathways from the results of WGCNA, such as pathogen identification pathways, MAPK signaling pathways, plant hormone signal transduction pathways, biosynthetic pathways and energy metabolism pathways.

Conclusion

Our results revealed that the NBS gene degenerations are common in the genus Dendrobium, which is the main reason for the diversity of NBS genes, and the NBS-LRR genes generally take part in D. officinale ETI system and signal transduction pathways. In addition, the D. officinale NBS-LRR gene Dof020138, which may have an important breeding value, is indirectly activated by SA in the ETI system.
Sedative effect and safety of different doses of S-ketamine in combination with propofol during gastro-duodenoscopy in school-aged children: a prospective, randomized study
Authors: Wang Junxia , Hu Weidong , Zhao Xianliang , Ren Weilian , Huang Xin , Zhang Bin
Published: November 2022

Background

Propofol combined with opioids can reduce the dosage of propofol and improve the safety of endoscopy. However, there are few studies on propofol combined with S-ketamine in children undergoing gastro-duodenoscopy. We aim to determine the sedative effect and safety of different doses of S-ketamine in combination with propofol in school-aged children undergoing gastro-duodenoscopy.

Methods

This is a prospective, randomized trial. Totally, 120 school-aged children who underwent gastro-duodenoscopy were randomly allocated into Group P, Group S0.3, Group S0.5 and Group S0.7. During induction, children in Group P, Group S0.3, Group S0.5 and Group S0.7 received 0, 0.3 mg.kg−1, 0.5 mg.kg−1 and 0.7 mg.kg−1 S-ketamine, respectively, following 3 mg.kg−1 propofol injection. During gastro-duodenoscopy, 1 mg.kg−1 of propofol was added according to the condition of the children and the BIS (bispectral index) value. The primary outcome was smooth placement rate of the first endoscope insertion. The secondary outcome was the times of additional propofol, the total amount of propofol, adverse events, recovery time, length of PACU (post anesthesia care unit) stay and endoscopist satisfaction.

Results

The smooth placement rate of the first endoscope insertion in Group P, Group S0.3 and Group S0.5 was significantly lower than that in Group S0.7 (16.70%, 34.50%, 50.00% vs. 83.30%, respectively, P < 0.001). The times of additional propofol in Group S0.3 (P = 0.018), Group S0.5 (P = 0.014) and Group S0.7 (P = 0.001) were significantly less than Group P. The total amount of propofol in Group S0.7 was significantly less than Group P (P < 0.001). The incidence of intraoperative hypotension in Group S0.5 and Group S0.7 was low. Group S0.7 had significantly higher incidence of postoperative dizziness (P = 0.003), longer PACU stay (P = 0.018) and higher endoscopist satisfaction (P = 0.001) than Group P. There was no difference in the recovery time among groups.

Conclusion

S-ketamine (0.7 mg.kg−1) in combination with propofol can provide satisfactory sedative effect and reduce the dosage of propofol in school-aged children undergoing gastro-duodenoscopy, but there are higher incidence of postoperative dizziness and longer PACU stay.
Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma
Authors: Li Lincheng , Xiao Zhaohui , He Pengyi , Zou Wenbo , Deng Zhaoda , Zhang Gong , Liu Rong
Published: November 2022

Background

Transient receptor potential (TRP) channels have high permeability to Ca2+ ions because they are non-selective ion channels. TRP channels have been implicated in tumor onset and progression, proliferation, and migration in recent years. However, the prognostic value of genes related to TRP and their specific mechanism in pancreatic adenocarcinoma (PAAD) are yet to be understood.

Methods

Public databases such as TCGA and GEO were used to retrieve data on gene expression and clinical information of patients with pancreatic adenocarcinoma for our study. ConsensusClusterPlus package was used for unsupervised clustering analysis. The microenvironment cell population (MCP)-counter approach was employed to measure the immune cells infiltration status. The Pearson correlation was performed to identify TRP-associated lncRNAs.

Results

Initially, we separated PAAD patients into three clusters depending on TRP-related genes, and of the three clusters, cluster B showed the least immune cell infiltration, which was correlated with poor prognosis. Moreover, GSVA enrichment analysis further revealed that cluster A was subjected to a considerable enrichment in carcinogenic signaling pathways, whereas cluster C was enriched in immune-related pathways. Then, using TRP-associated lncRNAs as a starting point, we constructed a prognostic risk model for PAAD patients that could efficiently predict their prognosis. Further, GSEA revealed that cancer-related pathways, for instance, the cell cycle, p53 signaling pathway, etc. were considerably enriched in the high-risk group. In addition, we looked into the link between the prognostic model and the immunological microenvironment. Lower cytotoxic lymphocytes, NK cells, CD8 T cells, and endothelial cells infiltration were found to be associated with high risk using the MCP-counter algorithm. The expression of CD274, POLE2, MCM6, and LOXL2 was also found to be higher in the high-risk group. TMB was also considerably greater in high-risk individuals, indicating that immune checkpoint inhibitors (ICIs) therapy may benefit them more. Lastly, qRT-PCR further confirmed the differential expression of these prognostic TRP-associated lncRNAs, indicating that these lncRNAs play an imperative role in PAAD tumorigenesis.

Conclusion

TRP family genes may represent a new class of candidate molecular markers of the occurrence and progression of PAAD. Risk models based on TRP-associated lncRNAs could provide important new references for immunotargeted therapy of pancreatic adenocarcinoma.