bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased LTB4 metabolites and PGD2 in BAL fluid after methacholine challenge in asthmatic subjects
Authors: Nowak D , Grimminger F , Jorres R , Oldigs M , Rabe KF , Seeger W , Magnussen H
Published: November 2022

The bronchoconstrictor potency of inhaled methacholine is widely used to assess airway responsiveness. However, evidence has accumulated that methacholine inhalation challenge may lead to an inflammatory response in the lower respiratory tract. We therefore compared cellular, leukotriene and prostanoid profiles in bronchoalveolar lavages (BAL) obtained five hours after methacholine challenge to control lavages without prior challenge. Eight subjects with asymptomatic to mild bronchial asthma and nine nonatopic healthy controls were enrolled in the study. Without prior challenge, the percentage of BAL eosinophils was higher in the asthmatic subjects ((mean +/- SD), 1.1 +/- 0.9%) than in the control subjects (0.1 +/- 0.1%. Leukotriene B4 (LTB4), and its omega-oxidation products (20-OH-LTB4 and 20-COOH-LTB4) were the only leukotrienes detectable in the baseline BAL fluids in five of the eight asthmatic patients. After methacholine challenge, no change in BAL cell profile occurred, but in the asthmatic patients, the total amounts of LTB4 and its omega-oxidation products rose from 0.52 +/- 0.50 ng.ml-1 (pre-challenge) to 1.55 +/- 1.32 ng.ml-1 (post-challenge), and prostaglandin D2 (PGD2) rose from 49.1 +/- 15.7 (pre-challenge) to 94.4 +/- 25.4 pg.ml-1 (post-challenge), with no change in 6-keto-PGF1 alpha, thromboxane B2 (TXB2), and prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2). In the healthy controls, no consistent change in BAL cell profile and mediators occurred after methacholine provocation. We conclude that inhaled methacholine stimulates LTB4 and PGD2 release in asthmatics, but not in healthy controls, without affecting the number of inflammatory cells in BAL fluid.
Pulmonary veno-occlusive disease and Hodgkin's lymphoma
Authors: Swift GL , Gibbs A , Campbell IA , Wagenvoort CA , Tuthill D
Published: November 2022

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension, and is of unknown aetiology. It has seldom been described in association with malignant disease and cytotoxic chemotherapy, and there have been only two previous reports of an association with Hodgkin's disease [1, 2]. We report a third case which developed 14 yrs after Hodgkin's disease had been diagnosed and treated, initially with radiotherapy and subsequently with chemotherapy.
Importance of the time interval between FEV1 measurements in a methacholine provocation test
Authors: Malmberg P , Larsson K , Sundblad BM , Zhiping W
Published: November 2022

We examined the hypothesis that a forced expiratory volume in one second (FEV1) manoeuvre (and the preceding deep inhalation) before inhalation of methacholine might influence FEV1 measured after methacholine, if the time between measurements was short. Six to nine healthy subjects inhaled a single dose of methacholine, known to cause about 20% decrease in FEV1, on different days in different test protocols. If an FEV1 manoeuvre was performed immediately before methacholine, the first FEV1 measured 3 min after provocation was higher (77% of basal FEV1) than if a pre-methacholine FEV1 manoeuvre was not performed (64%). This effect of a pre-methacholine FEV1 manoeuvre was also demonstrated at 2, 4 and 6, but not at 10 min after the start of methacholine inhalation. If an FEV1 manoeuvre was not performed before methacholine, the second and subsequent FEV1 measured in constricted airways was higher than the first, and of similar magnitude to the first FEV1 in tests where a pre-challenge FEV1 manoeuvre was performed. In another trial, 10 healthy subjects performed two stepwise methacholine tests, with either 6 or 3 min between dose steps. The percentage decrease in FEV1 per mg of inhaled methacholine decreased from 2.6 (1.9-5.2) to 1.7 (0.8-2.3) (median, interquartile-range) when the time interval was shortened. The results suggest that the deep inhalation associated with the FEV1 manoeuvre decreases the bronchial tone in airways constricted by methacholine for up to 6 min, possibly due to yielding of cross-links in airway smooth muscles.
Immunoprotective behaviour of liposome entrapped cell wall subunit of Mycobacterium tuberculosis against experimental tuberculous infection in mice
Authors: Chugh IB , Khuller GK
Published: November 2022

We wanted to determine the immunoprotective behaviour of cell wall protein peptidoglycan complex (CW-PPC) of Mycobacterium tuberculosis H37Ra, using liposomes as adjuvant, in an experimental animal model. Immunization of mice with CW-PPC entrapped in liposomes induced both humoral response, as measured by enzyme-linked immunosorbent assay (ELISA), and cell-mediated immune responses, as seen by delayed type hypersensitivity (DTH) and leucocyte migration inhibition (LMI) techniques. Ten days after complete immunization, the animals were challenged with median lethal dose (LD50) of M. tuberculosis H37Rv. The animals exhibited significant protection, as evident by 72% survival after 30 days of infection, compared to 38% survival in control animals. Protective effect of immunization with liposome entrapped CW-PPC was further substantiated by significant decrease in the number of viable bacilli in lungs, liver and spleen of immunized animals, as compared to control animals. These results indicate that immunization with liposome-entrapped mycobacterial cell wall protein peptidoglycan complex induces protection against experimental tuberculosis.
Dynamics of eosinophil infiltration in the bronchial mucosa before and after the late asthmatic reaction
Authors: Aalbers R , de Monchy JG , Kauffman HF , Smith M , Hoekstra Y , Vrugt B , Timens W
Published: November 2022

We wanted to determine whether changes in bronchial hyperresponsiveness (BHR) following allergen challenge show a time relationship with inflammatory events in the airways of allergic asthmatic subjects. Lavage was performed and endobronchial biopsies were taken via the fiberoptic bronchoscope, before, and 3 and 24 h after, allergen challenge, on separate occasions, in nine dual asthmatic responders. The numbers of activated eosinophils, identified by immunohistochemistry, using the monoclonal anti-eosinophil cationic protein antibody, EG2, were significantly increased both at 3 h and at 24 h in the submucosa and bronchial lavage. A significant negative correlation was found between the number of EG2+ cells in the submucosa and in the bronchial lavage 24 h after the allergen challenge (r = -0.70). At 24 h, the amount of eosinophil cationic protein (ECP) was increased in the bronchial lavage. A significant correlation was observed between the amount of ECP at 3 h and the log provocative dose of house dust mite producing a 20% fall in forced expiratory volume in one second (PD20 HDM) (r = -0.63). The results suggest a recruitment of activated eosinophils to the submucosa and, further, to the epithelial lining, followed by degranulation. This process has already started 3 h after allergen challenge, and lasts for at least 24 h, which may result in mucosal damage and subsequent allergen-induced increase in BHR, before and after the late asthmatic reaction.
The medical management of patients with cystic fibrosis following heart-lung transplantation
Authors: Madden BP , Kamalvand K , Chan CM , Khaghani A , Hodson ME , Yacoub M
Published: November 2022

Transplantation for end-stage respiratory failure in cystic fibrosis (CF), with encouraging medium-term results, is now possible. This paper details the postoperative medical treatment required by these patients. The management of 79 patients who underwent heart-lung transplantation is described. Details of intensive care, postoperative care, long-term follow-up, and the problems specific for cystic fibrosis patients are reported. The duration of care in the Intensive Care Unit (ICU) was 1-93 days (median 5 days). Intubation was required for 7 h to 93 days (median 48 h), and 11 patients required haemodiafiltration. High doses of cyclosporin A (mean 22 mg.kg-1 q.d.) were required. Acute rejection was common. There were 133 episodes of infection: bacterial 115, viral 11, and other organisms 7. Grand mal seizures occurred in 10 patients, lymphoproliferative disorders in 4, and obliterative bronchiolitis in 17. The median duration of hospital stay was 32 days. Despite having a multi-system disease, patients with CF can be successfully transplanted, if detailed attention is paid to their complex medical management.
Surfactant inhibition by plasma proteins: differential sensitivity of various surfactant preparations
Authors: Seeger W , Grube C , Gunther A , Schmidt R
Published: November 2022

Leakage of plasma proteins into the alveolar space may inhibit surfactant function. We compared the surface properties and the sensitivity to inhibitory proteins of different organic solvent surfactant extracts and a synthetic surfactant. Experiments were performed in the pulsating bubble surfactometer, with surfactant concentrations ranging between 0.1 and 2 mg.ml-1. Inhibition profiles towards fibrinogen, albumin and haemoglobin were obtained from calf lung surfactant extracts (CLSE), Alveofact, Curosurf and Survanta (all used in clinical, replacement studies in respiratory distress syndrome (RDS) and of an apoprotein-based synthetic phospholipid mixture (PLM-C/B; DPPC:PG:PA = 68.5:22.5:9, supplemented with 2% wt/wt non-palmitoylated human recombinant SP-C and 1% t/wt natural bovine SP-B). In the absence of inhibitory proteins, all surfactants exhibited dose-dependent rapid adsorption (rank order of relative efficacy PLM-C/B = CLSE > Alveofact > Curosurf > Survanta). Minimal surface tension was reduced to near zero values under dynamic compression (rank order PLM-C/B > CLSE > Alveofact = Curosurf) and to approximately 4 mN.m-1 (Survanta). Curosurf and Survanta were dose-dependently inhibited by fibrinogen > haemoglobin > albumin, with far-reaching loss of surface activity at protein-surfactant ratios above 1:1. In contrast, CLSE and Alveofact were only moderately inhibited by fibrinogen, and were not affected by haemoglobin and albumin, up to protein-surfactant ratios of 2:1. PLM-C/B exhibited resistance to fibrinogen, intermediate sensitivity to albumin, and was severely inhibited by haemoglobin. We conclude that various natural surfactant extracts and an apoprotein-based synthetic surfactant mixture markedly differ in their sensitivity to inhibitory plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac role in exercise limitation in asthmatic subjects with special reference to disease severity
Authors: Varray A , Mercier J , Savy-Pacaux AM , Prefaut C
Published: November 2022

We wanted to assess limitations in cardiorespiratory fitness of asthmatic subjects, acclimatized to 1,300 m altitude and in a clinically stable state. We therefore studied 16 young asthmatic and 8 normal young subjects during an incremental bicycle exercise test. The asthmatics were divided into two groups, according to the Aas classification: a moderate asthma group (degree 2 and 3, no pulmonary impairment during symptom-free intervals), and a severe asthma group (degree 4 and 5, with persistent airway obstruction). The results showed that cardiorespiratory fitness is limited in severe asthmatic subjects acclimatized to an altitude of 1,300 m, due to decreased cardiac output and stroke volume. At submaximal exercise, the lower stroke volume is compensated by an increased arteriovenous oxygen content difference, but this compensation no longer exists at maximal exercise, which explains the lower maximal oxygen uptake in the severe asthma group. The hypothesis that the high tidal volume in the severe asthma group could lead to a decrease in left ventricular performance is considered. In conclusion, with respect to cardiorespiratory response to exercise, asthmatics should not be considered as a homogeneous group. Furthermore, relationship between ventilatory requirement and its consequences upon cardiac stroke volume provides a strong argument for the physical rehabilitation of asthmatics. Indeed, aerobic training can decrease the ventilation level for a given workload, and thus reduce inappropriate adaptations to exercise.
Lack of short-term effect of the thromboxane synthetase inhibitor UK-38,485 on airway reactivity to methacholine in asthmatic subjects
Authors: Gardiner PV , Young CL , Holmes K , Hendrick DJ , Walters EH
Published: November 2022

Previous open studies have suggested that thromboxane receptor antagonists or synthesis inhibitors lower airway hyperresponsiveness in human subjects. This would indicate a role of thromboxane A2 in the development or maintenance of hyperresponsiveness in asthma. Ten nonsmoking asthmatics (aged 23-64 yrs, 9 male) were included in a randomized, double-blind, placebo-controlled, cross-over study of the effect of one week of treatment with a potent selective thromboxane synthetase inhibitor (UK-38,485, 600 mg daily) on airway responsiveness. The study was preceded by a two week run-in period, and two weeks were used for wash-out between the two trial periods. Adequacy of dosage and patient compliance was confirmed by a reduction in the ex vivo formation of thromboxane B2 (median concentration 3.22 micrograms.ml-1 after placebo, 0.10 microgram.ml-1 after UK-38,485, p < 0.05). The mean forced expiratory volume in one second (FEV1) after UK-38,485 was 2.55 l, compared to 2.56 l after treatment with placebo (p = 0.74). The geometric mean provocative dose of methacholine producing a 20% fall in FEV1 (PD20) before and after UK-38,485 was 23.9 and 32.2 micrograms, respectively, compared to 25.1 and 26.3 micrograms respectively, before and after placebo (p = 0.31). The results of this study suggest that thromboxane A2 does not play an important role in the maintenance of increased airway responsiveness in moderately severe asthmatics treated with low doses of inhaled steroids.
Ba 679 Br, a new long-acting antimuscarinic bronchodilator: a pilot dose-escalation study in COPD
Authors: Maesen FP , Smeets JJ , Costongs MA , Wald FD , Cornelissen PJ
Published: November 2022

Preclinical studies with Ba 679 Br have demonstrated a significantly longer duration of action than ipratropium bromide. Following inhalation of single doses, no systemic antimuscarinic effects were noted at doses likely to be bronchodilating in man. The objective of the present pilot-study of Ba 679 Br was to establish the dose-range for its bronchodilatory activity in a small number of chronic obstructive pulmonary disease (COPD) patients, before initiating a formal dose- and time-response study. Employing an open cross-over design, the efficacy of Ba 679 Br was tested, following single inhalational administration of five doses of increasing magnitude on separate days in six patients with COPD. A piezoelectric crystal was used, in order to nebulize an aqueous solution into a mist suitable for inhalation. There was a mean increase in forced expiratory volume in one second (FEV1) of 36% 30 min after inhaling ipratropium bromide 40 micrograms. Pulmonary function tests (FEV1, and specific airways conductance (sGaw)) were performed, at regular time intervals up to 24 h after test drug inhalation. The bronchodilatory activity of Ba 679 Br appeared to be dose-related in the dose-range tested (10-160 micrograms). A peak response was reached in 1.5-2 h, and persisted for 10-15 h in the majority of patients with return to baseline FEV1 approximately 19 h after dosing. No changes in physical examination, electrocardiogram (ECG) and laboratory safety tests from predose values were noted, and no serious adverse events were reported by the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Leucocyte-endothelial adhesion molecules and their role in bronchial asthma and allergic rhinitis
Authors: Montefort S , Holgate ST , Howarth PH
Published: November 2022

Leucocyte-endothelial adhesion molecules are involved in the initial stages of the recruitment and migration of inflammatory leucocytes from the circulation to sites of inflammation. There is accumulating evidence for their involvement in the pathophysiology of airway mucosal allergic inflammation, such as that found in asthma and rhinitis. The best characterized adhesion molecule families are the integrins, the immunoglobulin supergene family and the selectins. This review article describes some of the characteristics and properties of these families. We also discuss the situations in which these adhesion molecules might be involved in inflammatory airway diseases, and how evidence for this role might lead to future modes of therapy for these common conditions.
Asymptomatic solitary papilloma of the bronchus: review of occurrence in Japan
Authors: Miura H , Tsuchida T , Kawate N , Konaka C , Kato H , Ebihara Y
Published: November 2022

A case of solitary papilloma of the bronchus is described, and 15 other cases occurring in Japan are reviewed. A 57 year old asymptomatic male was referred to our hospital because many squamous metaplastic cells with moderate atypia were observed in sputum cytology, twice in 3 months. The chest X-ray showed no abnormal findings. Endoscopic examination revealed a polypoid tumour at the bifurcation of the right B6a and B6b. The tumour was removed completely by endoscopic biopsy, and histological findings showed squamous papilloma. There has been no evidence of recurrence for 3 yrs. We are not aware of a previously reported case of bronchial papilloma without symptoms or abnormal shadow on chest X-ray. Considering the fact that malignant change was reported in only one case in Japan, and that there is a possibility of cancer subsequently developing at another location in the lung which might also require resection, lobectomy should be avoided if the tumour can be removed completely through endoscopy. If the lesion is limited to a small area in the bronchus, conservative treatment such as photodynamic therapy and/or yttrium aluminium garnet (YAG) laser vaporization might be sufficient to obtain a complete cure.
Extracellular and intracellular magnesium concentrations in asthmatic patients
Authors: de Valk HW , Kok PT , Struyvenberg A , van Rijn HJ , Haalboom  , Kreukniet J , Lammers JW
Published: November 2022

Magnesium deficiency is associated with increased contractility of smooth muscle cells. Since contractility of bronchial smooth muscle is important in patients with asthma, magnesium deficiency could negatively influence the clinical condition. We wanted to assess whether magnesium deficiency exists in patients with asthma. Extracellular (plasma) and intracellular (erythrocytes and mononuclear leucocytes) concentrations of magnesium were determined in 20 mildly symptomatic patients with asthma and compared to 20 healthy controls. In asthmatic patients, the mean +/- SD magnesium level in plasma was 0.81 +/- 0.05 mmol.l-1, in erythrocytes 0.20 +/- 0.02 fmol.cell-1, and in mononuclear leucocytes 5.10 +/- 2.55 fmol.cell-1; these values did not differ significantly from those of the healthy controls: 0.79 +/- 0.06 mmol.l-1, 0.19 +/- 0.02 fmol.cell-1, and 4.61 +/- 1.75 fmol.cell-1, respectively. No evidence for the existence of a magnesium deficit needing chronic magnesium supplementation was, thus, found in these patients.
Tobacco smoke exposure suppresses radiation-induced inflammation in the lung: a study of bronchoalveolar lavage and ultrastructural morphology in the rat
Authors: Bjermer L , Cai Y , Nilsson K , Hellstrom S , Henriksson R
Published: November 2022

Previous studies on patients with breast cancer, who received postsurgical irradiation, displayed a markedly suppressed inflammatory response in the lung of smoking patients compared to nonsmokers. The aim of the present study was to investigate further the effect of exposure to tobacco smoke on the development of irradiation-induced pneumonitis in the rat. Four groups of animals were used: controls (C); those exposed to tobacco smoke (S); those irradiated but not exposed to smoke (RNS); and those irradiated and exposed to tobacco smoke (RS). The rats were exposed to a diluted main stream of cigarette smoke, at a concentration of about 0.4 mg.l-1, in a nose-only exposure system for 1 h.day-1, 5 days.week-1 for 10 weeks. Exposure to tobacco smoke started 3 weeks before irradiation. The basal one third of both lungs was exposed to a single radiation dose of 28 Gy (6 MeV photons). All animals were killed 7 weeks after irradiation. We compared findings in bronchoalveolar lavage (BAL) and tissue morphology. The alveolar tissue showed less inflammation in the RS-group than in the RNS-group. Most strikingly, mast cells were increased one hundredfold in the lung interstitium and thirty fold in the peribronchial area in the RNS-group, whereas no increase was found in the RS-group or in the controls. The alveolar septa of the RNS-group were thickened, with occurrence of inflammatory cells and mast cells, whereas the RS-group displayed no difference as compared to the non-irradiated, nonsmoking group (C).(ABSTRACT TRUNCATED AT 250 WORDS)
Non-Hodgkin's lymphoma presenting as multiple cavitating pulmonary nodules
Authors: Van Schoor J , Joos G , Pauwels R
Published: November 2022

Intrathoracic involvement is common in non-Hodgkin's lymphoma (NHL). We present the case of a young woman with a secondary pulmonary lymphoma (SPL) of the centroblastic subtype, with B-cell characteristics. The chest radiograph at presentation revealed an extremely rare pattern of multiple cavitating pulmonary nodules. The radiographic patterns of intrathoracic NHL are discussed.
The distribution of adhesive mechanisms in the normal bronchial epithelium
Authors: Montefort S , Baker J , Roche WR , Holgate ST
Published: November 2022

The integrity of the bronchial epithelium is dependent on various adhesion mechanisms that serve to hold the composite structure of the epithelium together and anchor it to the underlying basement membrane. Using immunohistochemistry we wanted to map out a number of these junctional and non-junctional adhesion mechanisms in the normal human bronchial epithelium. The beta 1-associated integrin subunit alpha 2 was immunolocalized to all of the epithelial intercellular spaces, whilst alpha 6 and beta 4 were strongly evident at the basal cell layer basement membrane junction. The alpha 1 and alpha 5 integrin subunits were not detected anywhere in the epithelium. Monoclonal antibodies (MoAbs) to tight junction polypeptides and the E-cadherin, liver cell adhesion molecule (LCAM), immunolocalized to the apicolateral portions of the intercellular junctions between all neighbouring columnar cells, with LCAM extending further along the lateral cell membrane. Desmosomal protein (dp) 1 and 2 MoAbs gave a punctate pattern between all of the suprabasal cells, and exhibited the greatest intensity of staining at the junction between the columnar and basal cell layers. In conclusion, there is an organized distribution of adhesive mechanisms within the normal human bronchial epithelium, which may be targeted by the various insults which lead to epithelial shedding.
Quantitative importance of asbestos as a cause of lung cancer in a Swedish industrial city: a case-referent study
Authors: Jarvholm B , Larsson S , Hagberg S , Olling S , Ryd W , Toren K
Published: November 2022

We wanted to assess the quantitative importance of asbestos as a cause of lung cancer. In a case-referent study, the exposure to asbestos, tobacco smoke and some other occupational exposures were compared between 147 cases of lung cancer (100 men, 47 women), 111 hospital referents, and 109 population referents, all below the age of 75 yrs and living in an industrial city. The attributable risk of lung cancer due to asbestos exposure was 16% in men (95% confidence interval 1-31%). No woman had occupational exposure to asbestos. We conclude that in the mid 1980's tobacco smoking was the major attributable risk, being 95% for men and 78% for women, but that in men asbestos was an appreciable contributing factor in the general population of a Swedish industrial city.
Plasma lactate dehydrogenase: a marker of disease activity in cryptogenic fibrosing alveolitis and extrinsic allergic alveolitis?
Authors: Matusiewicz SP , Williamson IJ , Sime PJ , Brown PH , Wenham PR , Crompton GK , Greening AP
Published: November 2022

Total plasma lactate dehydrogenase (LDH) activity may be elevated in cryptogenic fibrosing alveolitis (CFA) and extrinsic allergic alveolitis (EAA), and may be a useful monitor of disease progress. In a retrospective, primary referral centre study, we compared LDH at presentation, prior to bronchoalveolar lavage BAL, and after treatment and follow-up with changes in pulmonary function, in patients with CFA, EAA and pulmonary sarcoidosis. Plasma levels of LDH at presentation in CFA (n = 47) and EAA (n = 10) were significantly higher than in patients with sarcoidosis (n = 36). LDH activity decreased in patients with improving lung function (EAA, p = 0.008; CFA, p = 0.02), whereas it increased in CFA patients with deteriorating lung function (p = 0.015). Total plasma LDH is a simple, though nonspecific test, which appears to reflect changes of disease activity in patients with CFA and EAA.
The phenotype of alveolar macrophages and its correlation with immune cells in bronchoalveolar lavage
Authors: Striz I , Wang YM , Svarcova I , Trnka L , Sorg C , Costabel U
Published: November 2022

The phenotype of alveolar macrophages (AMs) is known to be modulated during pathological immune reactions in the lung. In this study, we wanted to determine the relationship between the AM phenotype and changes in the proportions of the various immune cells in bronchoalveolar lavage (BAL). BAL was performed in 76 consecutive patients, including 32 with sarcoidosis, 8 with idiopathic pulmonary fibrosis, 9 with pneumoconiosis, 13 with other respiratory disorders, and 14 controls without evidence of interstitial lung disease. The phenotype of AMs was studied by a panel of 15 monoclonal antibodies against various myeloid antigens, and was correlated with the proportions of cells obtained by BAL. The percentage of BAL lymphocytes showed a relationship with the expression of macrophage antigens in 11 out of 15 antigens studied (all except adhesive molecules CD11a, CD11c, CD18 and the antigen 25F9 present on mature macrophages). Furthermore, the CD4/CD8 ratio of BAL T-lymphocytes correlated with the AM expression of CD54 (intercellular adhesion molecule-1 (ICAM-1)), RFD1 (marker of dendritic cells), and CD71 (transferrin receptor). In samples with an increased number of bronchoalveolar neutrophils, the subpopulation of 27E10 positive AMs (inflammatory acute phase macrophages) was increased. Eosinophils in BAL were not associated with a significant increase in AM membrane antigen expression. Prominent changes of the AM phenotype were found in active sarcoidosis showing lymphocytic alveolitis, with more frequent expression of CD54, KiM2, CD71, CD11b and RFD9. In conclusion, this study shows that the phenotype of AMs is related to the type and intensity of the immunopathological reaction in the lung, and correlates with the proportions of bronchoalveolar cells.
Bronchoalveolar lavage phospholipid abnormalities in HIV-infected patients
Authors: Escamilla R , Prevost MC , Cariven C , Hermant C , Krempf M , Chap H
Published: November 2022

Our aim was to evaluate the quality of pulmonary surfactant, a nonspecific defence system, during the course of human immunodeficiency virus) infection. Protein and phospholipid composition were determined in 127 bronchoalveolar lavage (BAL) fluids from 89 HIV seropositive patients (54 acquired immune deficiency syndrome (AIDS), 35 non-AIDS) and 11 healthy controls. In all of the HIV BAL samples, biochemical abnormalities were found. In subjects with pulmonary infection or Kaposi's sarcoma, the phospholipid/protein ratio was decreased, mainly because of elevated protein levels (15.8 and 20, respectively, vs 7.2 mg.100 ml-1 for controls, p < 0.05). In subjects without obvious pulmonary involvement, phospholipid was decreased (1.3 +/- 0.2 vs 2.9 +/- 0.3 mg.100 ml-1 for controls, p < 0.001), whereas the protein was not altered. Phospholipid composition was also altered: the phosphatidylcholine percentage was decreased, whilst the other main phospholipids were increased. We conclude that the alveolar lining is altered, whatever the stage of HIV disease. In most patients, it results from an increase of vascular permeability, with an influx of serum proteins. However, changes in phospholipid composition suggest that, in some cases, surfactant is also altered.
Selenium deficiency augments the pulmonary toxic effects of oxygen exposure in the rat
Authors: Hawker FH , Ward HE , Stewart PM , Wynne LA , Snitch PJ
Published: November 2022

Selenium (Se) is a component of the antioxidant enzyme glutathione peroxidase (GSHPx). We wanted to determined whether Se deficiency predisposes to pulmonary O2 toxicity. Sixteen weanling rats were fed a Se-free diet (Se-). Sixteen rats fed the same diet had drinking water supplemented with 400 micrograms.l-1 sodium selenite (Se+). After 5 weeks, rats were killed after exposure to either 95% O2 or air for 36 h. Se concentration in blood, lung, liver, heart, muscle and spleen, and blood GSHPx activity were higher in Se+ than in Se- groups. Pulmonary oedema developed in both O2-exposed groups, but was more severe in Se-O2 group than in the Se+O2 group, as judged by the presence of pleural effusions (7 out of 8 versus 0 out of 8), elevated lavage protein concentration (173 +/- 17 versus 120 +/- 14 micrograms.ml-1), and higher wet/dry weight ratio (W:D) (5.8 +/- 0.07 versus 5.4 +/- 0.07). W:D correlated inversely with lung Se content in O2-exposed rats. Both O2-exposed groups had a reduction in the amount of less aggregated lavage phospholipid (PL) compared with the Se+air group. However, the Se-O2 group had increased total PL, because of an increase in more aggregated PL. We conclude that Se deficiency exacerbates pulmonary injury in O2-exposed rats, and that O2 toxicity is associated with an altered physical form of alveolar surfactant.
Frequency dependence of elastance and resistance in ventilated children with and without the chest opened
Authors: Nicolai T , Lanteri CJ , Sly PD
Published: November 2022

Measurements of respiratory mechanics in mechanically-ventilated children are potentially useful for understanding the pathogenesis and progress of diseases resulting in respiratory failure. Measurement techniques that can be simply and noninvasively employed model the respiratory system as a single compartment. The frequency dependence of elastance and resistance, both of the total respiratory system and of the lungs, was investigated in eight children (aged 2-56 months) undergoing open-heart surgery. The children were studied whilst anaesthetized, paralysed and mechanically-ventilated. Dynamic elastance (Ers) and resistance (Rrs) of the respiratory system and of the lung (EL, RL) were calculated using a multilinear regression technique, with the chest wall intact, prior to the commencement of surgery, and with the chest wall opened via a mid-line sternotomy. Measurements were repeated after brief (60 s) changes in ventilation frequency. The total respiratory system and the lungs demonstrated frequency-dependent behaviour, with elastance increasing and resistance decreasing with frequency. The pattern of the frequency-dependent behaviour was essentially the same, whether the chest wall was intact or opened, suggesting that the chest wall was not solely responsible for this behaviour in these children. These data are consistent with a linear viscoelastic model containing a Kelvin body. When using measurements of respiratory mechanics to follow the progress of respiratory disease in mechanically-ventilated children, this frequency-dependent behaviour must be taken into account.
Reversible hypercapnia in acute exacerbations of chronic obstructive pulmonary disease (COPD)
Authors: McNally E , Fitzpatrick M , Bourke S , Costello R , McNicholas WT
Published: November 2022

We prospectively studied emergency hospitalizations due to acute exacerbations of chronic obstructive pulmonary disease (COPD) among 74 hypercapnic patients, in order to determine factors which predict reversal to normocapnia as a result of therapy. Clinical, arterial blood gas and pulmonary function data on presentation were compared to predischarge values among those 58 patients who survived the admission. Patients were divided into those who reverted to normocapnia (reversible, 40% of surviving patients), and those who remained hypercapnic (chronic, 60% of surviving patients). Reversible patients had higher admission arterial oxygen tension (PaO2) levels than those with chronic hypercapnia (6.4 +/- 1.3 kPa (mean +/- SD), as compared to 5.7 +/- 1.1 kPa) better pulmonary function (forced expiratory volume in one second (FEV1) 35 +/- 16% predicted, as compared to 26 +/- 7.9), and a lower prevalence of cor pulmonale (30% as compared to 63% of patients). No admission variable(s) distinguished individual patients as reversible or chronic hypercapnic, and, in particular, admission arterial carbon dioxide tension (PaCO2) and pH levels were similar in both groups. Furthermore, there were no differences between survivors and those 16 patients who died during the admission, apart from a higher urea level among those who died. These findings suggest that reversible patients have milder underlying disease than those with chronic hypercapnia. Our data establish the high prevalence of reversible hypercapnia among patients hospitalized with exacerbations of COPD, and, furthermore, indicate that patients who are normocapnic in the stable state can develop similar levels of hypercapnia during exacerbations as those with chronic hypercapnia.
Pulmonary immune cells in health and disease: lymphocytes
Authors: Agostini C , Chilosi M , Zambello R , Trentin L , Semenzato G
Published: November 2022

Immunological defence mechanisms of the lung are provided by several different types of immunocompetent cell. Among these, the most important are lymphocytes, alveolar macrophages and neutrophils. This review focuses mainly on the pattern of physiological activities of pulmonary lymphocytes in the local host defences. The article provides an overview of the events leading to the recruitment, homing and activity of lymphocytes in the lower respiratory tract. The pathways through which the pulmonary lymphoid system recognizes, destroys and contributes to removing potentially harmful inhaled antigenic materials are also briefly discussed. The final section of the article highlights the pathogenetic role envisaged for lymphoid cells in disease states, in the context of the known biology of these cells.
Investigative use of fibreoptic bronchoscopy for local airway challenge in asthma
Authors: Makker HK , Montefort S , Holgate S
Published: November 2022

Local airway challenge has advantages over inhalation bronchial challenge as the response of the airway can be restricted and directly observed. It has been safely performed in subjects with mild or moderate asthma, either by the direct instillation of challenge solution to the selected segmental airways via a bronchoscope, or delivered to an airway segment isolated with a double-balloon catheter. However, these techniques carry potential complications, such as generalized wheeze, and due care is required in selection of subjects. Most investigators have used the method for studying the airway events following allergen challenge. Others have studied the airway changes following challenge with non-allergen provocation agents, such as hypertonic saline, adenosine 5'-monophosphate and cold dry air. The method has helped to define changes in the inflammatory cells and mediators in relation to early and late airway responses to allergen. Similarly, study of airway events following local challenge with hypertonic solution has provided useful knowledge in understanding the mechanisms of exercise-induced asthma. With more experience and an improved margin of safety, it will be possible to study local changes in airway physiology following local airway challenge. Finally, the techniques also have potential use for studying the airway events following provocation with a wide range of agents of potential relevance to the pathogenesis of asthma.
Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol
Authors: Pearce N , Weiland S , Keil U , Langridge P , Anderson HR , Strachan D , Bauman A , Young L , Gluyas P , Ruffin D , et al.
Published: November 2022

There is a need for a standardized approach to international and regional comparisons of the prevalence and severity of asthma, and for the monitoring of asthma morbidity over time. In 1991, standardized written and video questionnaires were developed and administered in surveys of schoolchildren, aged 12-15 yrs, in five regions in four countries: Adelaide, Australia (n = 1,428); Sydney, Australia (n = 1519); West Sussex, England (n = 2,097); Bochum, Germany (n = 1928); and Wellington, New Zealand (n = 1863). The self-reported prevalence of wheezing during the previous 12 months was similar in West Sussex (29% using the written questionnaire and 30% using the video questionnaire), Wellington (28 and 36%), Adelaide (29 and 37%), and Sydney (30 and 40%), but was lower in Bochum (20 and 27%). The one year prevalence of severe wheezing limiting speech was greater in Wellington (11%), Adelaide (10%) and Sydney (13%), than in West Sussex (7%) and Bochum (6%). The self-reported one year prevalences of frequent attacks, frequent nocturnal wheezing, and doctor diagnosed asthma, were also higher in the Australasian centres than in the European centres. We conclude, that an international comparison of asthma symptom prevalence in childhood, using simple standardized instruments, is feasible. Possible explanations for the differences in reported asthma severity between the Australasian and European centres include differences in exposure to risk factors and differences in the management of asthma.
Effect of oral terfenadine on bronchoconstrictor response to inhaled neurokinin A and histamine in asthmatic subjects
Authors: Crimi N , Oliveri R , Polosa R , Pulvirenti G , Prosperini G , Palemo F , Mistretta A
Published: November 2022

Neurokinin A (NKA) elicits a potent contractile effect in asthmatic airways. Its mechanism of action in bronchial asthma is still unknown. Recent work supports the view that NKA may stimulate mediator release from mast cells. To investigate the relative contribution of mast cell degranulation to the action of NKA, a randomized, double-blind study has been undertaken, to evaluate the effect of a potent and selective histamine H1-receptor antagonist, terfenadine (180 mg q.d., for three days), on bronchoconstriction provoked by inhaled NKA in six asthmatic subjects. Bronchial provocation tests with histamine were included in this study as control challenge. In the subjects studied, oral terfenadine, when compared to placebo, significantly increased the geometric mean (range) provocation dose of inhaled histamine required to reduce forced expiratory volume in one second (FEV1) by 20% of baseline (PD20) from 0.05 (0.03-0.08) mg (0.16 (0.10-0.26) mumol) to 1.19 (0.63-2.04) mg (3.88 (2.05-6.64) mumol). However, terfenadine failed to increase the airway responsiveness to NKA in all of the subjects studied, the geometric mean (range) PD15 NKA value being 0.94 (0.47-2.49) micrograms (8.36 (4.14-21.9 nmol) and 0.75 (0.48-1.59) micrograms (6.62 (4.23-14.0) nmol) after placebo and terfenadine, respectively. We conclude that NKA is a potent bronchoconstrictor agonist in asthma, being approximately 19 times more potent than histamine in molar terms. In this study on a small number of subjects, pharmacological intervention with oral terfenadine failed to achieve significant protection of the airways against the constrictor effect of NKA.(ABSTRACT TRUNCATED AT 250 WORDS)
Therapeutic equivalence between bambuterol, 10 mg once daily, and terbutaline controlled release, 5 mg twice daily, in mild to moderate asthma
Authors: Fugleholm AM , Ibsen TB , Laxmyr L , Svendsen UG
Published: November 2022

Bambuterol is the first long-acting oral beta 2-agonist with a 24 h effective duration. In order to investigate the possibility of replacing established treatment modalities with bambuterol once daily, we wanted to compare the bronchodilating and tremorogenic effects of bambuterol, 10 mg once daily, and terbutaline, 5 mg controlled-release (CR) tablets twice daily. The study was of a double-blind, double-dummy, randomized, cross-over design and involved two, two week treatment periods, separated by a one week wash-out period. Peak expiratory flow (PEF) recorded in patients' diaries was the primary efficacy variable. Seventy adult, asthmatic out-patients with mild to moderate asthma were included (forced expiratory volume in one second (FEV1) > or = 50% predicted). After treatment with bambuterol, mean morning and evening PEF (SD) were 347 (122) and 365 (121) l.min-1, respectively and 346 (121) and 365 (122) l.min-1, respectively, after treatment with terbutaline. FEV1 (SD) was 2.21 (0.91) l and 2.27 (0.93) l after bambuterol and terbutaline treatments, respectively. Tremor scores tended to be lower during treatment with bambuterol, although not significantly so. Tremor scores were low, in general. In conclusion, no difference in the bronchodilating effect was demonstrated between bambuterol, 10 mg once daily, and controlled release terbutaline, 5 mg twice daily. A tendency towards less tremor was seen with bambuterol.
Attenuation of chronic hypoxic pulmonary hypertension in rats by cyclooxygenase products and by nitric oxide
Authors: Russell P , Wright C , Kapeller K , Barer G , Howard P
Published: November 2022

We wanted to assess the respective roles of arachidonic acid products and nitric oxide in the modulation of pulmonary hypertension in chronically hypoxic rats. In isolated blood-perfused lungs, the effects of arachidonic acid before and after treatment with the cyclooxygenase inhibitor, meclofenamate, were compared in control (C) rats and rats exposed for two weeks to 10% oxygen (chronic hypoxia CH). Arachidonic acid caused mixed dilator and constrictor effects during both normoxia and hypoxia; dilatation was more prominent in chronically hypoxic rats. Meclofenamate abolished both dilator and constrictor actions of arachidonic acid; it raised baseline, normoxic pulmonary artery pressure, in chronically hypoxic but not control rats, which suggests that dilator products of arachidonic acid are released in the pulmonary hypertension of chronic hypoxia and attenuate pulmonary artery pressure. As shown previously, the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) raised pressure in chronically hypoxic but not control rats. Meclofenamate and L-NAME given in sequence both raised pulmonary artery pressure in chronically hypoxic rats and the combined rise was substantial (+13 mmHg). We conclude that, in the conditions of our experiment, both nitric oxide and dilator prostanoids are released in hypoxic pulmonary hypertension in rats. Thus, two synthetic processes, both possibly endothelial dependent, may modulate hypoxic pulmonary hypertension.
Pulmonary immune cells in health and disease: polymorphonuclear neutrophils
Authors: Sibille Y , Marchandise FX
Published: November 2022

The pulmonary vasculature represents the largest reservoir of polymorphonuclear neutrophils (PMNs) in the human body. This is in striking contrast with the paucity of PMNs present in the normal airways and alveoli. However, the respiratory tract constitutes an easy access for microorganisms and particles present in inhaled air and, therefore, efficacious defence mechanisms are required. When the mucociliary clearance and the alveolar macrophages are over-whelmed, the rapid recruitment of PMNs from the lung vasculature appears to be a crucial response of the host against the pathogens. The regulation of adherence of PMNs to endothelial cells (EC), followed by the transendothelial migration are now better understood, and are under the control of a series of adhesion molecules modulated by bacterial and inflammatory mediators. In addition to their defensive role, PMNs have also been implicated in acute and chronic injurious diseases of the lung. Clearly, PMNs contain enough cytotoxic and proteolytic material to induce lesional changes. However, the release of this material is likely to be dependent on environmental factors, including mediators derived from other inflammatory and immune cells. The presence or absence of these factors could explain the fact that high numbers of PMNs can be observed in the airways and alveoli without major lesions whilst in other conditions, a marginal increase of PMNs in the respiratory tract can be associated with major damage and irreversible architectural changes in the lung.
Fatal asthma attributed to patent foramen ovale
Authors: Boon ES , Maesen BL , Valcke Y , Koudstaal J
Published: November 2022

A 37 year old woman was admitted to the hospital with acute severe asthma, shortly followed by respiratory failure and circulatory arrest. Despite intensive cardio-pulmonary resuscitation, during which extreme arterial hypoxaemia persisted, the patient died. Postmortem examination revealed a patent foramen ovale, with a diameter of 1 cm. A severe right-to-left shunt, initiated by acute pulmonary hypertension, was considered to be the cause of death. Because of the relatively high prevalence of patent foramen ovale in the normal population, we suggest this patency may enhance the risk of fatal outcome of acute severe asthma.
Tracheobronchial amyloidosis with hilar lymphadenopathy associated with a serum monoclonal immunoglobulin
Authors: Crestani B , Monnier A , Kambouchner M , Battesti JP , Reynaud P , Valeyre D
Published: November 2022

We report a case of amyloidosis, restricted to the lower respiratory tract, with prominent tracheobronchial involvement and bilateral hilar lymphadenopathy, associated with a monoclonal serum protein of the immunoglobulin G (IgG) lambda type. The careful search for an extrathoracic site of involvement was negative. This particular association has not been reported previously.
A novel bi-directional heterogeneous network selection method for disease and microbial association prediction
Authors: Guan Jian , Zhang Zhao Gong , Liu Yong , Wang Meng
Published: November 2022

Microorganisms in the human body have a great impact on human health. Therefore, mastering the potential relationship between microorganisms and diseases is helpful to understand the pathogenesis of diseases and is of great significance to the prevention, diagnosis, and treatment of diseases. In order to predict the potential microbial disease relationship, we propose a new computational model. Firstly, a bi-directional heterogeneous microbial disease network is constructed by integrating multiple similarities, including Gaussian kernel similarity, microbial function similarity, disease semantic similarity, and disease symptom similarity. Secondly, the neighbor information of the network is learned by random walk; Finally, the selection model is used for information aggregation, and the microbial disease node pair is analyzed. Our method is superior to the existing methods in leave-one-out cross-validation and five-fold cross-validation. Moreover, in case studies of different diseases, our method was proven to be effective.